Affinage

IL25

Interleukin-25 · UniProt Q9H293

Length
177 aa
Mass
20.3 kDa
Annotated
2026-04-28
100 papers in source corpus 47 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-25 (IL-17E) is an epithelial- and tuft-cell-derived cytokine that orchestrates type 2 immunity, tissue remodeling, metabolic regulation, and neuroimmune signaling through its heterodimeric IL-17RA/IL-17RB receptor. IL-25 engages the adaptor Act1/CIKS via a TRAF4–SMURF2–DAZAP2 regulatory cascade and signals through NF-κB, MAPKs (ERK, JNK, p38), and a distinct Act1-independent STAT5 pathway to drive Th2 cytokine production (IL-4, IL-5, IL-13), ILC2 activation, MPPtype2 progenitor expansion, and IL-9 induction, while simultaneously suppressing Th17 responses through IL-13-mediated inhibition of dendritic cell IL-23 expression (PMID:11058597, PMID:11754819, PMID:19155511, PMID:25681341, PMID:25821217, PMID:17200411, PMID:20154671). In barrier tissues, tuft-cell-derived IL-25 sustains ILC2 homeostasis and feeds back through IL-13 to promote tuft cell and goblet cell differentiation, forming a self-amplifying epithelial remodeling circuit that is critical for helminth defense and contributes to allergic airway inflammation, pulmonary fibrosis, and colorectal tumor-permissive microenvironments (PMID:26675736, PMID:24344271, PMID:35658010, PMID:34932383). Beyond immunity, IL-25 promotes beige adipogenesis via macrophage catecholamine production, suppresses innate antiviral interferon responses in airway epithelium, and modulates social behavior through IL-17RB-expressing cortical neurons (PMID:34351905, PMID:35508632, PMID:40199322).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    Identification of IL-25 as a cytokine that binds IL-17RB and activates NF-κB established it as a functional member of the IL-17 family with a discrete receptor, resolving its ligand-receptor pairing and initial signaling output.

    Evidence Receptor-ligand binding assays and NF-κB reporter assays in transfected cells

    PMID:11058597

    Open questions at the time
    • Signaling intermediates between receptor and NF-κB not identified
    • In vivo function unknown
  2. 2001 High

    In vivo administration and transgenic overexpression demonstrated that IL-25 drives a potent Th2-type immune response (IL-4, IL-5, IL-13, eosinophilia, IgE), establishing its non-redundant role as a type 2 immune initiator distinct from other IL-17 family members.

    Evidence Recombinant IL-25 infusion and transgenic overexpression in mice with serum cytokine, immunoglobulin, and histopathology readouts

    PMID:11714825 PMID:11754819

    Open questions at the time
    • Cellular targets mediating Th2 induction incompletely defined
    • Endogenous cellular sources of IL-25 unknown
  3. 2006 High

    Dissection of downstream signaling revealed that IL-25 receptor engagement activates NF-κB and all three MAPK branches through TRAF6, and that IL-25-induced airway hyperresponsiveness depends on IL-13/IL-4Rα/STAT6, defining the essential effector arm.

    Evidence TRAF6-knockout MEFs, dominant-negative TRAF6, and IL-13/IL-4Rα/STAT6-knockout mice with IL-25 challenge

    PMID:16393988 PMID:17177681

    Open questions at the time
    • Role of adaptor proteins such as Act1 not yet tested
    • Whether TRAF6 is the sole TRAF involved unclear
  4. 2007 High

    IL-25-deficient mice revealed a dual immunomodulatory role: loss of IL-25 exacerbated autoimmune Th17 pathology (EAE) through derepression of DC-derived IL-23, establishing the IL-25→IL-13→DC suppression→Th17 inhibition axis and showing IL-25 is not solely a type 2 amplifier.

    Evidence IL-25-knockout mice in EAE model with cytokine neutralization and DC cytokine profiling

    PMID:17200411

    Open questions at the time
    • Whether IL-25 directly acts on DCs or requires intermediate cells not fully resolved
    • Relevance to human autoimmune disease untested
  5. 2009 High

    Identification of Act1/CIKS as the essential signaling adaptor for IL-25-mediated allergic inflammation, and of CD11c+ lung macrophages and IL-17RB+ iNKT cells as key IL-25-responsive innate effectors, resolved major questions about signal transduction and target cell identity.

    Evidence Act1-knockout mice with IL-25 challenge; adoptive transfer of IL-17RB+ vs IL-17RB− iNKT cells into iNKT-deficient mice

    PMID:19155511 PMID:19342692

    Open questions at the time
    • How Act1 is recruited to the IL-25 receptor complex mechanistically unknown
    • Whether additional adaptor-independent pathways exist not addressed
  6. 2010 High

    Discovery that IL-25 elicits a novel multipotent progenitor (MPPtype2) population and directly induces IL-9 via IL-17RB on T cells expanded the downstream effector repertoire beyond classical Th2 cytokines and ILC2 activation.

    Evidence IL-25 injection with MPPtype2 phenotyping, adoptive transfer rescue in Il25−/− mice; retroviral IL-17RB overexpression driving IL-9 in T cells

    PMID:20154671 PMID:20200520

    Open questions at the time
    • Transcriptional programs distinguishing MPPtype2 from ILC2 only partially characterized
    • Whether IL-9 induction requires Act1 unknown
  7. 2015 High

    Three breakthroughs refined IL-25 mechanism: (1) TRAF4 was shown to bridge Act1 to IL-25R by recruiting SMURF2 to degrade the inhibitor DAZAP2; (2) an Act1-independent STAT5 pathway was discovered via direct STAT5 recruitment to IL-17RB tyrosine residues; (3) tuft cells were identified as the constitutive intestinal source of IL-25 driving an ILC2–IL-13–epithelial remodeling circuit essential for helminth defense.

    Evidence TRAF4-KO mice with co-IP and siRNA; IL-17RB tyrosine mutagenesis with conditional STAT5 KO; tuft-cell ablation and lineage tracing in helminth-infected mice

    PMID:25681341 PMID:25821217 PMID:26675736

    Open questions at the time
    • Structural basis of STAT5–IL-17RB interaction not determined
    • Relative contributions of Act1-dependent vs STAT5-dependent arms in different cell types not quantified
    • Signals initiating tuft-cell IL-25 secretion incompletely understood
  8. 2018 High

    Extension of the tuft-cell paradigm to airway brush cells and thymic mTEC IV, plus the finding that leukotriene E4 acts upstream through CysLT3R to expand tuft cells and amplify IL-25 output, established IL-25-producing tuft/chemosensory cells as a conserved feature across mucosal barriers.

    Evidence CysLT3R-KO and LTC4 synthase-KO mice with aeroallergen challenge; single-cell RNA-seq of thymic epithelium in Pou2f3-KO mice; sinonasal SCC identification by flow cytometry and immunofluorescence

    PMID:29778504 PMID:30022162 PMID:30291131

    Open questions at the time
    • Whether thymic IL-25 functionally regulates T cell selection unknown
    • CysLT3R–IL-25 axis not validated in human tissue
  9. 2020 High

    Studies defining BATF as selectively required for IL-25-responsive inflammatory ILC2s, and IKK-mediated Regnase-1 degradation as a checkpoint for IL-25-driven ILC2 activation, resolved how IL-25-specific ILC2 subsets are transcriptionally programmed and post-transcriptionally licensed.

    Evidence BATF-KO mice with helminth infection and RNA-seq; Regnase-1 phospho-mutant knock-in mice with IL-25 lung challenge

    PMID:31924686 PMID:31990689

    Open questions at the time
    • Direct mRNA targets of Regnase-1 in ILC2s not fully catalogued
    • Whether BATF is a direct transcriptional target of IL-25 signaling unknown
  10. 2020 High

    Demonstration that mTOR suppresses autophagy-mediated IL-25 production in airway epithelium, and that IL-25 modulates keratinocyte proliferation and motility via IL-17RA/IL-17RB, revealed upstream metabolic regulation and autocrine/paracrine functions in epithelial homeostasis beyond immune cell activation.

    Evidence Airway-epithelium-specific mTOR knockdown with LC3B-KO rescue; keratinocyte 2D/3D culture with time-lapse imaging and actin cytoskeleton analysis

    PMID:31958433 PMID:33077617

    Open questions at the time
    • Molecular cargo within autophagosomes that controls IL-25 release not identified
    • Whether keratinocyte autocrine IL-25 signaling operates in vivo untested
  11. 2021 High

    IL-25 was found to promote beige adipogenesis through macrophage-derived catecholamines and to create tumor-permissive microenvironments in colorectal cancer via ILC2-sustained MDSCs, extending its functions beyond classical mucosal immunity into metabolism and cancer immunoevasion.

    Evidence IL-4Rα blockade and clodronate depletion in HFD mice measuring UCP1 and tyrosine hydroxylase; IL-25 signaling ablation in Apc-mutant mice with therapeutic anti-IL-25 antibody

    PMID:34351905 PMID:35658010

    Open questions at the time
    • Whether IL-25 acts directly on adipocyte precursors or exclusively through macrophages not resolved
    • Whether anti-IL-25 therapy is effective in established human CRC unknown
  12. 2022 High

    IL-25 blockade during rhinovirus infection restored type I/III interferon responses and reduced viral load, establishing IL-25 as an active suppressor of innate antiviral immunity in airway epithelium and providing a mechanistic link between type 2 cytokine circuits and viral susceptibility.

    Evidence Anti-IL-25 mAb (LNR125) treatment in differentiated bronchial epithelial cells and in vivo rhinovirus model with transcriptomic and viral load analysis

    PMID:35508632

    Open questions at the time
    • Molecular mechanism by which IL-25 suppresses IFN gene transcription not defined
    • Applicability to other respiratory viruses beyond rhinovirus untested
  13. 2025 High

    Brain-wide mapping revealed IL-25 expression by cortical neurons and IL-17RB-mediated signaling in cortical circuits that enhances social interaction behavior, establishing a neuroimmune function for IL-25 independent of peripheral immunity.

    Evidence Brain-wide receptor mapping, single-cell RNA-seq, in situ hybridization, and behavioral assays with genetic manipulation in mice

    PMID:40199322

    Open questions at the time
    • Downstream neuronal signaling pathways activated by IL-25/IL-17RB unknown
    • Whether peripheral IL-25 accesses the brain or only locally produced IL-25 is relevant not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of the IL-25/IL-17RA/IL-17RB ternary complex, the relative in vivo contributions of Act1-dependent versus STAT5-dependent pathways across cell types, and the mechanisms by which IL-25 suppresses interferon responses and modulates neuronal circuits remain unresolved.
  • No crystal or cryo-EM structure of IL-25 receptor complex
  • Act1-dependent vs STAT5-dependent pathway partitioning across tissues not quantified
  • Neuronal IL-25 signaling mechanism undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-168256 Immune System 8 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3
Partners
ACT1IL17RAIL17RBTRAF2BTRAF4NR6TRAF6

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 IL-25 (IL-17E) was identified as a novel cytokine and ligand for the receptor IL-17Rh1 (EVI27/IL-17BR). Binding of IL-25 to IL-17Rh1 induces NF-κB activation and stimulates production of the proinflammatory chemokine IL-8. Receptor-ligand binding assay, NF-κB reporter assay, IL-8 production assay The Journal of biological chemistry High 11058597
2001 Infusion of IL-25 into mice induced expression of IL-4, IL-5, and IL-13, resulting in Th2-like responses (elevated IgE, IgG1, IgA, blood eosinophilia, mucus production, epithelial hyperplasia). IL-25 was shown to act on MHC class II-high, CD11c-dull, lineage-negative accessory cells to promote type 2 cytokine production. In vivo cytokine infusion, gene expression analysis, flow cytometry, ELISA Immunity High 11754819
2001 Forced overexpression of murine IL-17E (IL-25) in transgenic mice induced a Th2-biased response (eosinophilia, elevated IgE/IgG1, elevated IL-13 and IL-5), neutrophilia via G-CSF induction, and pathological changes in multiple tissues including liver, heart, and lungs. Transgenic mouse overexpression, serum cytokine measurement, histopathology Journal of immunology High 11714825
2002 Transgenic overexpression of human IL-17E (IL-25) in mice resulted in eosinophilia, B-lymphocyte hyperplasia, elevated IgE/IgM/IgG, and upregulation of IL-17Rh1 (IL-17BR/Evi27) receptor in transgenic tissues, confirming IL-25 as a regulator of hematopoietic and immune functions favoring Th2-type responses. Transgenic mouse overexpression, flow cytometry, in situ hybridization, ELISA Blood High 12239140
2006 IL-25 receptor (IL-17BR) cross-linking activates NF-κB and MAPK pathways (ERK, JNK, p38). TRAF6, but not TRAF2, associates with IL-25R even in the absence of ligand and is required for IL-25R-mediated NF-κB activation and downstream gene expression (IL-6, TGF-β, G-CSF, TARC), as demonstrated in TRAF6-deficient MEFs and by dominant-negative TRAF6. Co-immunoprecipitation, dominant-negative overexpression, TRAF6-knockout MEFs, NF-κB reporter assay, MAPK phosphorylation assay Journal of immunology High 16393988
2006 Human lung fibroblasts constitutively express IL-17BR (the IL-25 receptor), and IL-25 stimulation upregulates proinflammatory mediators (CCL-5, CCL-11, GM-CSF, CXCL-8), with synergistic induction of GM-CSF and CXCL-8 in combination with TNF-α, implicating IL-25 in eosinophilic airway inflammation via structural cells. Western blot, RT-PCR, ELISA, immunofluorescence, primary human lung fibroblasts The Journal of allergy and clinical immunology Medium 16522458
2006 TNF-α upregulates IL-17BR expression in airway smooth muscle cells via NF-κB, while IFN-γ downregulates it via the ERK pathway. IL-25 stimulation of airway smooth muscle cells increases expression of ECM components (procollagen-αI, lumican), suggesting a proremodeling role. RT-PCR, kinase inhibitor studies, airway smooth muscle cell cultures American journal of physiology. Lung cellular and molecular physiology Medium 16428271
2006 IL-25-induced airway hyperresponsiveness (AHR) and pulmonary inflammation are dependent on IL-13 and its signaling through IL-4Rα and STAT6, as demonstrated by significantly reduced AHR in IL-13-/-, IL-4Rα-/-, and STAT6-/- mice treated with IL-25. Gene-knockout mouse models (IL-13-/-, IL-4Rα-/-, STAT6-/-), in vivo IL-25 intratracheal instillation, lung function measurement Clinical and experimental allergy High 17177681
2007 IL-25 regulates autoimmune inflammation by suppressing Th17 responses: IL-25-deficient mice are highly susceptible to EAE with increased IL-23 and IL-17-producing T cells. IL-25 acts through IL-13 induction, which directly inhibits IL-23, IL-1β, and IL-6 expression in dendritic cells, thereby suppressing Th17 responses. IL-25-knockout mice, EAE model, cytokine neutralization, cytokine ELISA, flow cytometry The Journal of experimental medicine High 17200411
2007 IL-25 promotes expansion and Th2 cytokine production of Th2 central memory cells stimulated by TSLP-activated DCs or TCR engagement. This is associated with sustained GATA-3, c-MAF, and JunB expression in an IL-4-independent manner. Activated eosinophils and basophils are identified as cellular sources of bioactive IL-25 protein in humans. Human Th2 memory cell culture, TSLP-DC co-culture, flow cytometry, cytokine ELISA, cell sorting The Journal of experimental medicine High 17635955
2008 Commensal bacteria limit intestinal Th17 cell expansion through promoting IL-25 (IL-17E) expression by intestinal epithelial cells, which in turn inhibits macrophage-derived IL-23, establishing an IL-25–IL-23–IL-17 regulatory axis in the intestine. Germ-free mouse model, cytokine measurement, Th17 cell frequency analysis The Journal of experimental medicine High 18762568
2009 The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation, including eosinophil recruitment, mucus hypersecretion, Th2 cytokine production, and airway hyperreactivity. Act1 is also required to transmit IL-17 signals, despite distinct biological outcomes. CD11c+ macrophage-like lung cells were identified as physiologically relevant targets of IL-25 in vivo. Act1-knockout mice, in vivo IL-25 administration, flow cytometry, lung function assay Journal of immunology High 19155511
2009 IL-25 receptor (IL-17RB) is expressed on a subset of iNKT cells, and IL-17RB+ iNKT cells produce large amounts of Th2 cytokines that are enhanced by IL-25 stimulation. Adoptive transfer of IL-17RB+ but not IL-17RB- iNKT cells restores AHR in iNKT-deficient mice, and IL-25-induced AHR is impaired in iNKT-deficient mice. Flow cytometry, adoptive transfer, iNKT-deficient mice, intranasal IL-25 administration, airway hyperreactivity measurement Journal of immunology High 19342692
2009 IL-25 inhibits monocyte/macrophage inflammatory cytokine production induced by TLR ligands through a p38 MAPK-driven, SOCS-3-dependent mechanism. In vivo, IL-25 inhibits monocyte-derived cytokines and protects against LPS-induced lethal endotoxemia in mice. Primary human CD14+ cell culture, p38 MAPK inhibitor, SOCS-3 measurement, LPS endotoxemia mouse model Blood High 19129540
2010 IL-25 promotes the accumulation of lineage-negative multipotent progenitor (MPPtype2) cells (Sca-1+, c-Kitint) in gut-associated lymphoid tissue that promote Th2 cytokine responses. MPPtype2 cells exhibit multipotent capacity giving rise to monocyte/macrophage and granulocyte lineages. Adoptive transfer of MPPtype2 cells confers protective immunity to helminth infection in IL-25-deficient mice. IL-25 injection, cell phenotyping by flow cytometry, in vitro differentiation assay, adoptive transfer into Il25-/- mice, helminth infection model Nature High 20200520
2010 IL-25 signals through IL-17RB to regulate IL-9 expression in T cells. IL-25 treatment enhances IL-9 expression in TGF-β+IL-4-generated T cells that express IL-17RB. Transgenic and retroviral overexpression of IL-17RB in T cells results in IL-25-induced, IL-4-independent IL-9 production. This pathway regulates IL-9 in allergic airway inflammation in vivo. T cell culture with cytokines, retroviral overexpression of IL-17RB, transgenic mice, in vivo allergic airway model Nature immunology High 20154671
2013 IL-25 simultaneously elicits phenotypically and functionally distinct innate lymphoid cell (ILC2) and MPPtype2 cell populations. IL-33 elicits robust ILC2 responses while IL-25 predominantly promotes MPPtype2 cell responses. MPPtype2 cells differ from ILC2 in developmental requirements for specific transcription factors, genome-wide transcriptional profile, and functional potential. In vivo cytokine administration, flow cytometry, genome-wide transcriptional profiling, ILC2 depletion, functional assays The Journal of experimental medicine High 23960191
2015 Intestinal tuft cells constitutively express IL-25 to sustain ILC2 homeostasis. After helminth infection, tuft-cell-derived IL-25 activates ILC2s to secrete IL-13, which acts on epithelial crypt progenitors to promote differentiation of tuft and goblet cells. This IL-25-ILC2-epithelial circuit mediates type 2 immune remodeling in the small intestine. Cell-specific deletion/ablation in mice, helminth infection model, lineage tracing, flow cytometry, cytokine measurement Nature High 26675736
2015 TRAF4 is required for IL-25 signaling: IL-25R recruits TRAF4, which is required for ACT1/IL-25R interaction. TRAF4 then recruits the E3 ligase SMURF2 to degrade the IL-25R-inhibitory molecule DAZAP2. A tyrosine residue within IL-25R mediates DAZAP2 interference. Silencing Dazap2 increases ACT1/IL-25R interaction and IL-25 responsiveness. TRAF4-knockout mice, co-immunoprecipitation, siRNA silencing, in vivo IL-25 administration, lung inflammation assay Journal of immunology High 25681341
2015 IL-25 signals through a novel Act1-independent pathway via direct STAT5 activation. STAT5 is recruited to IL-25R (IL-17RB) in a ligand-dependent manner through unique tyrosine residues on IL-17RB. Conditional STAT5 deletion in T cells or epithelial cells leads to defective IL-25-initiated Th2 polarization and defective IL-25 enhancement of Th2 responses. Co-immunoprecipitation, conditional STAT5 knockout, site-directed mutagenesis of IL-17RB tyrosines, Th2 differentiation assays Journal of immunology High 25821217
2015 IL-25 protects against hepatic steatosis through IL-13 activation of STAT6. IL-25 administration to HFD-fed mice increases IL-13, promotes alternatively activated Kupffer cells/macrophages, and decreases lipid droplet proteins. This effect is absent in STAT6-deficient or IL-13-deficient mice. IL-13 (but not IL-25) directly downregulates lipid droplet proteins in primary hepatocytes. HFD mouse model, IL-25-/- mice, STAT6-/- mice, IL-13-/- mice, primary hepatocyte stimulation, ELISA, Western blot, histology Journal of immunology High 26423151
2016 Keratinocyte-derived IL-17E (IL-25) is overexpressed in psoriatic plaques, and macrophages take up IL-25 via receptor-mediated clathrin-dependent endocytosis rather than synthesizing it. M2, but not M1, macrophages express the IL-17E receptor and respond to IL-17E by producing inflammatory cytokines and chemokines involved in neutrophil recruitment. Immunofluorescence, flow cytometry, endocytosis inhibitor assays, ELISA, in vitro macrophage stimulation The Journal of investigative dermatology Medium 27329229
2018 Thymic tuft-like medullary epithelial cells (mTEC IV, identified by single-cell RNA-seq) constitutively express IL-25. Pou2f3-deficient mice lacking these tuft-like TECs show complete and specific depletion of mTEC IV, resulting in increased levels of thymus-resident ILC2s. Single-cell RNA-seq, spatial mapping, chromatin profiling, Pou2f3-knockout mice, flow cytometry Nature High 30022162
2018 Airway brush cells (tuft cells) are the dominant epithelial source of IL-25 and expand upon aeroallergen inhalation. This expansion is regulated by leukotriene E4 (LTE4) acting through CysLT3R on epithelial cells via an IL-25-dependent but STAT6-independent signaling pathway. Blockade of IL-25 attenuates CysLT3R-dependent type 2 lung inflammation. LTC4 synthase-/- mice, CysLT3R-/- mice, LTE4 inhalation model, IL-25 blockade, flow cytometry, STAT6 pathway analysis Science immunology High 30291131
2018 Solitary chemosensory cells (SCCs) expressing gustducin and DCLK1 are the predominant source of IL-25 in the human sinonasal epithelium. IL-13 exposure increases SCC proliferation and induces apical secretion of IL-25 in sinonasal epithelial cultures. Flow cytometry, immunofluorescence, ELISA, primary epithelial cell culture with IL-13 stimulation The Journal of allergy and clinical immunology Medium 29778504
2018 IL-25 induces pulmonary fibrosis via ILC2-derived IL-13, which drives collagen deposition in lungs. IL-13 release from ILC2s is sufficient for this effect in an innate, T-cell-independent manner. Murine fibrosis model, ILC2-specific experiments, collagen measurement, histology, cytokine blockade Proceedings of the National Academy of Sciences High 24344271
2018 IL-25 negatively regulates LPS-induced exosome release from macrophages by downregulating Rab27a and Rab27b expression, thereby suppressing exosome-induced TNF-α expression. This represents a crosstalk pathway between lung epithelial cells (source of IL-25) and alveolar macrophages. Transwell co-culture system, Western blot for Rab27a/b, exosome measurement, LPS stimulation, ELISA Military Medical Research Medium 30056803
2019 IL-25 promotes fibroblast-to-myofibroblast differentiation (increased α-SMA, fibronectin) and MMP-1/-13 expression in nasal polyp-derived fibroblasts via IL-17RB-dependent MAPK (ERK, p38, JNK) and NF-κB signaling pathways. siRNA knockdown of IL-17RB, MAPK and NF-κB inhibitors, Western blot, scratch assay, Sircol collagen assay PloS one Medium 28771607
2020 BATF is a transcription factor selectively required for IL-25-responsive inflammatory ILC2s (iILC2s, characterized as IL-17RBhigh, KLRG1high, BATFhigh, Arg1low) but not for tissue-resident ILC2s. BATF deficiency selectively impairs IL-25-mediated helminth clearance and iILC2 generation without affecting nILC2 frequency or function. BATF-knockout mice, RNA-seq, Nippostrongylus brasiliensis infection model, flow cytometry, intracellular cytokine staining Science immunology High 31924686
2020 MTOR suppresses autophagy-mediated IL-25 production in airway epithelial cells. MTOR knockdown in mouse bronchial epithelium increases IL-25 production and airway inflammation, while LC3B deletion abolishes this effect. IL-25 blockade attenuates exacerbated airway inflammation in MTOR-deficient mice. Airway-epithelium-specific MTOR knockdown mice, lc3b-/- mice, IL-25 neutralization, in vitro HBE cell stimulation Thorax High 33077617
2020 Regnase-1 negatively regulates ILC2 function, and IκB kinase (IKK) complex-mediated Regnase-1 degradation is essential for IL-33- and IL-25-induced ILC2 activation, including cell proliferation and type 2 cytokine (IL-5, IL-9, IL-13) production. Regnase-1AA/AA mice (with Regnase-1 resistant to IKK degradation) show attenuated IL-25-induced type 2 pulmonary inflammation. Regnase-1 phospho-mutant knock-in mice, in vitro ILC2 stimulation, RNA stability assay, in vivo papain/IL-25/IL-33 challenge models JCI insight High 31990689
2020 Keratinocytes express a complete IL-25 receptor (IL-17RA/IL-17RB) at their surface, with receptor expression further induced by IL-17A. IL-22 enhances IL-25 production in keratinocytes. IL-25 promotes keratinocyte proliferation, upregulation of differentiation-associated genes (keratin 10), and increases cell motility, speed, and displacement with specific actin cytoskeleton and cell-substrate adhesion changes. Flow cytometry, 2D and 3D keratinocyte culture, time-lapse cell imaging, immunofluorescence, gene expression analysis The Journal of investigative dermatology Medium 31958433
2020 IL-25 from keratinocytes signals through ILC2s to drive IL-13 production and epidermal hyperplasia, dermal CD4+ T cell infiltration, and cutaneous expression of IL-13 and TH2-attracting chemokines (CCL17, CCL22) at sites of allergic skin inflammation. Keratinocyte-specific IL-25 deletion and ILC2-specific IL-25R deletion both impair these responses. Cell-specific conditional knockout mice (keratinocyte-specific Il25 KO, ILC2-specific IL-25R KO), epicutaneous sensitization model, flow cytometry, IL-13-eGFP reporter mice The Journal of allergy and clinical immunology High 32179159
2021 Tuft cell-derived cysteinyl leukotrienes (CysLTs) and IL-25 act synergistically to initiate lung type 2 inflammation. LTC4 combined with subthreshold IL-25 synergistically activates inflammatory ILC2s and dendritic cells. Tuft-cell-specific deletion of Ltc4s reduces lung inflammation, and this is further enhanced by concomitant IL-25 blockade. Tuft-cell-specific Ltc4s conditional knockout, IL-25 blockade, aeroallergen challenge model, flow cytometry, cytokine measurement Science immunology High 34932383
2021 IL-25-ILC2 axis creates a cancer-permissive microenvironment in colorectal cancer by sustaining tumor-infiltrating MDSCs that suppress antitumor immunity. Ablation of IL-25 signaling reduces tumors and doubles life expectancy in APC-mutation-driven intestinal tumorigenesis. Therapeutic IL-25 antibody blockade decreases intratumoral ILC2s and MDSCs while increasing antitumor adaptive T cell and IFN-γ responses. Il25 signaling ablation in Apc-mutant mice, therapeutic antibody blockade, flow cytometry, survival analysis, ILC2 and MDSC quantification Science immunology High 35658010
2021 IL-25 induces ROS production in monocytes via mitochondrial complex I and II/III activity, subsequently activates AMPK, and induces mitophagy via the PINK1/Parkin pathway to stimulate M2 macrophage polarization. CCL-22 secretion (M2 marker) induced by IL-25 is suppressed by mitophagy inhibitors and PINK1 knockdown. Flow cytometry, Western blot, confocal microscopy, mitophagy inhibitors, PINK1 siRNA knockdown, ELISA International journal of molecular sciences Medium 35008429
2022 Macrophage migration inhibitory factor (MIF) is required for the IL-25-dependent tuft cell expansion circuit during helminth infection. MIF acts upstream of the ILC2-tuft cell circuit; administration of IL-25 fully compensates for MIF deficiency, restoring tuft cell differentiation and goblet cell responses. MIF receptor CXCR4 is expressed on ILC2s and macrophages. MIF-deficient mice, MIF inhibitor (4-IPP), IL-25 rescue administration, intestinal organoid cultures, flow cytometry Mucosal immunology High 35288645
2022 Indolepropionic acid (IPA) promotes expansion of intestinal tuft cells and increases IL-25 secretion both in vivo and ex vivo through the free fatty acid receptor 3 (FFAR3) pathway in tuft cells, contributing to colonic barrier integrity and ameliorating obesity-related metabolic disorders. In vivo IPA supplementation in HFD mice, ex vivo organoids, FFAR3 pathway analysis, tight junction protein measurement, IL-25 ELISA The FEBS journal Medium 35509122
2025 IL-25 (IL-17E) is expressed by cortical neurons in the brain, and signals through IL-17RB (and IL-17RA)-expressing neurons in the cortex to enhance social interaction behavior. Brain-wide mapping revealed region-specific expression of IL-17R subunits with IL-17RB—but not IL-17RC—playing a role in social behaviors. Brain-wide receptor mapping, single-cell RNA-seq, in situ hybridization, behavioral assays, genetic manipulation Cell High 40199322
2011 IL-25 causes caspase-mediated apoptosis in breast cancer cells that express high levels of IL-25R (IL-17RB), without affecting nonmalignant mammary epithelial cells that express low IL-25R. The differential cytotoxic activity is mediated by the differential expression of IL-25R. 3D culture system, apoptosis assays, caspase activation measurement, IL-25R expression analysis, cancer cell lines vs. non-malignant cells Science translational medicine Medium 21490275
2015 IL-17A and IL-25 (IL-17E) both activate c-RAF/ERK1/2/p70 S6 Kinase signaling in breast cancer cell lines, promote resistance to docetaxel, and induce generation of tumorigenic low molecular weight forms of cyclin E (LMW-E). Western blot for phosphorylation (c-RAF, ERK1/2, p70 S6K), drug resistance assay, breast cancer cell lines Scientific reports Medium 26154409
2016 IL-25 activates EGFR in TNBC cells via Src-dependent EGFR transactivation and promotes nuclear translocation of pSTAT3 and pEGFR by acting through IL-17RA/IL-17RB. IL-25 also activates PYK-2, Src, and STAT3 kinases and synergizes with EGF signaling. Western blot for phosphorylation, EGFR nuclear translocation assay, kinase inhibitors, breast cancer cell lines Oncotarget Medium 27462789
2018 IL-25 induces ER stress and epithelial apoptosis in airway epithelial cells via PERK pathway activation. IL-25-induced airway epithelial apoptosis and tight junction damage is dependent on PERK activity and can be inhibited by the ER stress inhibitor 4-PBA. In vitro airway epithelial cell culture with IL-25, ER stress markers (PERK), PERK inhibitor, 4-PBA inhibitor, tight junction protein measurement Scientific reports Medium 29784924
2020 IL-25 suppresses IL-22-induced osteoclastogenesis and RANKL expression in RA fibroblast-like synoviocytes through STAT3 and p38 MAPK/IκBα signaling pathways. Primary FLS culture, RANKL ELISA, osteoclastogenesis assay, Western blot for STAT3, p38 MAPK, IκBα Arthritis research & therapy Medium 32972460
2022 IL-25 promotes diabetic wound healing through M2 macrophage polarization and fibroblast activation via PI3K/AKT/mTOR and TGF-β/SMAD signaling pathways; these effects are blocked by LY294002 (PI3K inhibitor) and LY2109761 (TGF-β receptor inhibitor). Diabetic mouse wound model, THP-1 and HDF cell culture, flow cytometry, RT-qPCR, Western blot, pathway inhibitors International immunopharmacology Medium 35149293
2021 IL-25 promotes beige fat formation in white adipose tissue by inducing M2 macrophage alternative activation (via IL-4 and IL-13 release) that regulates sympathetic innervation and upregulates tyrosine hydroxylase to produce catecholamines (norepinephrine). Blockade of IL-4Rα or macrophage depletion with clodronate liposomes impairs IL-25-induced beige fat formation. IL-25 signaling experiments, IL-4Rα blockade, clodronate-liposome macrophage depletion, tyrosine hydroxylase measurement, UCP1 thermogenesis assay, HFD mouse model PLoS biology High 34351905
2022 IL-25 blockade re-calibrates antiviral immunity in rhinovirus-infected airway epithelial cells, increasing type I/III IFN expression and reducing type 2 immune gene expression. Exogenous IL-25 increases viral load with suppressed innate immunity, while in vivo anti-IL-25 treatment reduces IL-25/type 2 cytokine expression, increases IFN-β, and reduces lung viral load. Anti-IL-25 monoclonal antibody (LNR125), rhinovirus infection of differentiated bronchial epithelial cells, RNA transcriptome analysis, in vivo mouse model, viral load measurement Communications biology High 35508632

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 990 26675736
2001 IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 928 11754819
2013 A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. The Journal of experimental medicine 788 24323357
2007 IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. The Journal of experimental medicine 512 17635955
2010 IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses. Nature 455 20200520
2007 IL-25 regulates Th17 function in autoimmune inflammation. The Journal of experimental medicine 322 17200411
2013 IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis. Proceedings of the National Academy of Sciences of the United States of America 312 24344271
2001 IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1. The Journal of biological chemistry 312 11058597
2007 Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. The Journal of allergy and clinical immunology 308 17889290
2014 Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation. Science translational medicine 278 25273095
2018 Single-cell mapping of the thymic stroma identifies IL-25-producing tuft epithelial cells. Nature 261 30022162
2008 Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine. The Journal of experimental medicine 233 18762568
2015 Recent advances in epithelium-derived cytokines (IL-33, IL-25, and thymic stromal lymphopoietin) and allergic inflammation. Current opinion in allergy and clinical immunology 194 25479313
2010 Regulation of IL-9 expression by IL-25 signaling. Nature immunology 184 20154671
2016 Combinatorial targeting of TSLP, IL-25, and IL-33 in type 2 cytokine-driven inflammation and fibrosis. Science translational medicine 157 27147589
2001 Forced expression of murine IL-17E induces growth retardation, jaundice, a Th2-biased response, and multiorgan inflammation in mice. Journal of immunology (Baltimore, Md. : 1950) 148 11714825
2002 Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production. Blood 144 12239140
2018 The cysteinyl leukotriene 3 receptor regulates expansion of IL-25-producing airway brush cells leading to type 2 inflammation. Science immunology 141 30291131
2018 Solitary chemosensory cells are a primary epithelial source of IL-25 in patients with chronic rhinosinusitis with nasal polyps. The Journal of allergy and clinical immunology 137 29778504
2021 IL-25 (IL-17E) in epithelial immunology and pathophysiology. The Journal of allergy and clinical immunology 123 33485651
2010 NK cell deficiency predisposes to viral-induced Th2-type allergic inflammation via epithelial-derived IL-25. Journal of immunology (Baltimore, Md. : 1950) 118 20855881
2013 IL-25 simultaneously elicits distinct populations of innate lymphoid cells and multipotent progenitor type 2 (MPPtype2) cells. The Journal of experimental medicine 113 23960191
2009 The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation. Journal of immunology (Baltimore, Md. : 1950) 113 19155511
2017 IL-25 in allergic inflammation. Immunological reviews 98 28658555
2013 IL-25 downregulates Th1/Th17 immune response in an IL-10-dependent manner in inflammatory bowel disease. Inflammatory bowel diseases 94 23429464
2011 IL-25 causes apoptosis of IL-25R-expressing breast cancer cells without toxicity to nonmalignant cells. Science translational medicine 92 21490275
2006 Mechanism of interleukin-25 (IL-17E)-induced pulmonary inflammation and airways hyper-reactivity. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 92 17177681
2019 Intestinal dysbacteriosis-induced IL-25 promotes development of HCC via alternative activation of macrophages in tumor microenvironment. Journal of experimental & clinical cancer research : CR 91 31296243
2013 Macrophages as IL-25/IL-33-responsive cells play an important role in the induction of type 2 immunity. PloS one 91 23536877
2021 Tuft cell-produced cysteinyl leukotrienes and IL-25 synergistically initiate lung type 2 inflammation. Science immunology 90 34932383
2020 ILC2 activation by keratinocyte-derived IL-25 drives IL-13 production at sites of allergic skin inflammation. The Journal of allergy and clinical immunology 89 32179159
2011 IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation. The Journal of allergy and clinical immunology 89 21794904
2009 Induction of airway hyperreactivity by IL-25 is dependent on a subset of invariant NKT cells expressing IL-17RB. Journal of immunology (Baltimore, Md. : 1950) 84 19342692
2006 Involvement of TNF receptor-associated factor 6 in IL-25 receptor signaling. Journal of immunology (Baltimore, Md. : 1950) 83 16393988
2021 IL-25 Induced ROS-Mediated M2 Macrophage Polarization via AMPK-Associated Mitophagy. International journal of molecular sciences 79 35008429
2006 IL-17E upregulates the expression of proinflammatory cytokines in lung fibroblasts. The Journal of allergy and clinical immunology 77 16522458
2009 IL-17E, a proinflammatory cytokine, has antitumor efficacy against several tumor types in vivo. Cancer immunology, immunotherapy : CII 76 20012860
2015 IL-25/IL-33-responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa. The Journal of allergy and clinical immunology 73 26684290
2014 Clinical associations between IL-17 family cytokines and periodontitis and potential differential roles for IL-17A and IL-17E in periodontal immunity. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 73 25369802
2016 Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis. The Journal of investigative dermatology 70 27329229
2022 An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment for Apc mutation-driven intestinal tumorigenesis. Science immunology 69 35658010
2015 Mutual upregulation of endothelin-1 and IL-25 in atopic dermatitis. Allergy 69 25903653
2020 BATF acts as an essential regulator of IL-25-responsive migratory ILC2 cell fate and function. Science immunology 68 31924686
2013 IL-25 and IL-25 receptor expression on eosinophils from subjects with allergic asthma. International archives of allergy and immunology 68 24247484
2016 IL-25 and IL-33 induce Type 2 inflammation in basophils from subjects with allergic asthma. Respiratory research 67 26762527
2009 Pulmonary IL-17E (IL-25) production and IL-17RB+ myeloid cell-derived Th2 cytokine production are dependent upon stem cell factor-induced responses during chronic allergic pulmonary disease. Journal of immunology (Baltimore, Md. : 1950) 67 19828636
2006 IL-25 regulates the expression of adhesion molecules on eosinophils: mechanism of eosinophilia in allergic inflammation. Allergy 66 16792588
2018 Lung epithelial cell-derived IL-25 negatively regulates LPS-induced exosome release from macrophages. Military Medical Research 62 30056803
2022 IL-25 improves diabetic wound healing through stimulating M2 macrophage polarization and fibroblast activation. International immunopharmacology 60 35149293
2011 Reciprocal expression of IL-25 and IL-17A is important for allergic airways hyperreactivity. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 56 21722219
2013 IL-33, but not IL-25, is crucial for the development of house dust mite antigen-induced allergic rhinitis. PloS one 55 24205109
2021 Roles of IL-25 in Type 2 Inflammation and Autoimmune Pathogenesis. Frontiers in immunology 54 34122457
2017 Local IL-25 contributes to Th2-biased inflammatory profiles in nasal polyps. Allergy 54 28771767
2015 IL-17A and its homologs IL-25/IL-17E recruit the c-RAF/S6 kinase pathway and the generation of pro-oncogenic LMW-E in breast cancer cells. Scientific reports 50 26154409
2015 Interleukin (IL)-25: Pleiotropic roles in asthma. Respirology (Carlton, Vic.) 50 26699081
2009 Inhibition of monocyte-derived inflammatory cytokines by IL-25 occurs via p38 Map kinase-dependent induction of Socs-3. Blood 49 19129540
2015 Association between single nucleotide polymorphisms IL17RA rs4819554 and IL17E rs79877597 and Psoriasis in a Spanish cohort. Journal of dermatological science 48 26347322
2006 TNF-alpha and IFN-gamma inversely modulate expression of the IL-17E receptor in airway smooth muscle cells. American journal of physiology. Lung cellular and molecular physiology 46 16428271
2015 IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice. PloS one 45 25629516
2019 IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation. The Journal of investigative dermatology 44 30738055
2016 IL-25 Receptor Expression on Airway Dendritic Cells after Allergen Challenge in Subjects with Asthma. American journal of respiratory and critical care medicine 44 26625138
2014 Cytokines (interleukin-9, IL-17, IL-22, IL-25 and IL-33) and asthma. Advanced biomedical research 44 24949298
2013 IL-25 prevents and cures fulminant hepatitis in mice through a myeloid-derived suppressor cell-dependent mechanism. Hepatology (Baltimore, Md.) 44 23564603
2017 ILC2s activated by IL-25 promote antigen-specific Th2 and Th9 functions that contribute to the control of Trichinella spiralis infection. PloS one 41 28898280
2020 IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes. The Journal of investigative dermatology 40 31958433
2018 IL-33, IL-25 and TSLP contribute to development of fungal-associated protease-induced innate-type airway inflammation. Scientific reports 40 30575775
2016 IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner. Scientific reports 40 27812008
2011 Inhibition of colitis by IL-25 associates with induction of alternatively activated macrophages. Inflammatory bowel diseases 40 21688353
2018 Allergy immunotherapy restores airway epithelial barrier dysfunction through suppressing IL-25 -induced endoplasmic reticulum stress in asthma. Scientific reports 39 29784924
2008 Virulizin induces production of IL-17E to enhance antitumor activity by recruitment of eosinophils into tumors. Cancer immunology, immunotherapy : CII 39 18351336
2018 IL-25 enhances TH17 cell-mediated contact dermatitis by promoting IL-1β production by dermal dendritic cells. The Journal of allergy and clinical immunology 37 29522843
2018 Biological Properties and the Role of IL-25 in Disease Pathogenesis. Journal of immunology research 37 30345318
2022 Indolepropionic acid reduces obesity-induced metabolic dysfunction through colonic barrier restoration mediated via tuft cell-derived IL-25. The FEBS journal 36 35509122
2019 Combined blockade of IL-25, IL-33 and TSLP mediates amplified inhibition of airway inflammation and remodelling in a murine model of asthma. Respirology (Carlton, Vic.) 36 31610614
2015 IL-25 and IL-33 Contribute to Development of Eosinophilic Airway Inflammation in Epicutaneously Antigen-Sensitized Mice. PloS one 36 26230091
2014 IL-17E (IL-25) and IL-17RB promote respiratory syncytial virus-induced pulmonary disease. Journal of leukocyte biology 35 24407884
2014 High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis. PloS one 35 25136988
2020 Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway. Arthritis research & therapy 32 32972460
2019 IL-25 contributes to lung fibrosis by directly acting on alveolar epithelial cells and fibroblasts. Experimental biology and medicine (Maywood, N.J.) 32 30997832
2016 IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression. PLoS pathogens 32 27055194
2021 IL-25-induced shifts in macrophage polarization promote development of beige fat and improve metabolic homeostasis in mice. PLoS biology 31 34351905
2015 Role of IL-25 in Immunity. Journal of clinical and diagnostic research : JCDR 31 26023586
2015 TRAF4-SMURF2-mediated DAZAP2 degradation is critical for IL-25 signaling and allergic airway inflammation. Journal of immunology (Baltimore, Md. : 1950) 30 25681341
2020 MTOR suppresses autophagy-mediated production of IL25 in allergic airway inflammation. Thorax 29 33077617
2015 IL-25 or IL-17E Protects against High-Fat Diet-Induced Hepatic Steatosis in Mice Dependent upon IL-13 Activation of STAT6. Journal of immunology (Baltimore, Md. : 1950) 29 26423151
2021 CircNRIP1 Modulates the miR-515-5p/IL-25 Axis to Control 5-Fu and Cisplatin Resistance in Nasopharyngeal Carcinoma. Drug design, development and therapy 28 33536745
2017 Efficacy of melatonin, IL-25 and siIL-17B in tumorigenesis-associated properties of breast cancer cell lines. Life sciences 28 28624391
2016 The effect of calprotectin on TSLP and IL-25 production from airway epithelial cells. Allergology international : official journal of the Japanese Society of Allergology 28 27475624
2015 A novel IL-25 signaling pathway through STAT5. Journal of immunology (Baltimore, Md. : 1950) 28 25821217
2009 IL-25: a key requirement for the regulation of type-2 immunity. BioFactors (Oxford, England) 28 19449446
2025 Brain-wide mapping of immune receptors uncovers a neuromodulatory role of IL-17E and the receptor IL-17RB. Cell 27 40199322
2022 The IL-25-dependent tuft cell circuit driven by intestinal helminths requires macrophage migration inhibitory factor (MIF). Mucosal immunology 27 35288645
2021 Epithelial miR-206 targets CD39/extracellular ATP to upregulate airway IL-25 and TSLP in type 2-high asthma. JCI insight 27 33945508
2017 IL-25-induced activation of nasal fibroblast and its association with the remodeling of chronic rhinosinusitis with nasal polyposis. PloS one 27 28771607
2020 Regnase-1 degradation is crucial for IL-33- and IL-25-mediated ILC2 activation. JCI insight 26 31990689
2017 Crosstalk between human endometrial stromal cells and decidual NK cells promotes decidualization in vitro by upregulating IL‑25. Molecular medicine reports 26 29257317
2016 The role of IL-25 and IL-33 in chronic rhinosinusitis with or without nasal polyps. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 26 27522661
2016 IL-17E synergizes with EGF and confers in vitro resistance to EGFR-targeted therapies in TNBC cells. Oncotarget 25 27462789
2015 IL-25 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma model. Respiratory research 25 25889697
2022 IL-25 blockade augments antiviral immunity during respiratory virus infection. Communications biology 24 35508632