| 1988 |
Murine IL-5/TRF cDNA encodes a 133-amino-acid precursor; the secreted form is a homodimeric glycoprotein (~46 kDa, comprising ~25–30 kDa subunits) that triggers activated B cells for terminal differentiation into Ig-secreting cells (IgM, IgG1, IgA) and promotes B cell growth and IL-2 receptor induction. |
cDNA cloning, recombinant protein expression, functional B-cell differentiation assays, immunoprecipitation with specific mAbs |
Immunological reviews |
High |
3284812
|
| 1988 |
IL-5 acts specifically on mIgA-positive Peyer's patch B cells to promote terminal differentiation into IgA-secreting cells without driving cell proliferation, establishing that IL-5 is a differentiation (not proliferation) factor acting downstream of IgA isotype switching. |
Cell sorting of mIgA+ vs mIgA- B cells, rIL-5 stimulation, ELISPOT assay, [3H]thymidine incorporation |
Journal of immunology |
High |
3258891
|
| 1988 |
Recombinant EDF (IL-5) expressed in CHO cells retains its dimeric structure and biological activity identical to natural EDF, confirming the homodimeric architecture is sufficient for function. |
Recombinant expression in CHO DHFR- cells, methotrexate selection, biochemical characterization of secreted protein |
Biochemical and biophysical research communications |
Medium |
3348775
|
| 1991 |
Human eosinophils express a single class of high-affinity IL-5 receptor (Kd ~170–330 pM; ~260–380 sites/cell) with a molecular mass of 55–60 kDa identified by affinity cross-linking; IL-5 binding is inhibited by excess unlabeled IL-5 or anti-IL-5 mAb but not by other cytokines, demonstrating receptor specificity. |
Radiolabeled IL-5 binding assay, Scatchard analysis, affinity cross-linking, competition binding |
Cellular immunology |
High |
2015632
|
| 1992 |
The high-affinity receptors for IL-5, IL-3, and GM-CSF are heterodimers composed of a cytokine-specific α subunit and a shared common β subunit; the β subunit is required both for high-affinity ligand binding and for signal transduction, including tyrosine phosphorylation and Ras protein activation. In humans, a single common β subunit is shared among all three receptors. |
Molecular cloning of receptor subunits, reconstitution of high-affinity receptors, signal transduction assays |
International journal of cell cloning |
High |
1613263
|
| 1994 |
IL-5 is a homodimeric glycoprotein that signals through a heterodimeric receptor comprising a unique IL-5-specific α chain (required for ligand binding) and a common β chain shared with IL-3R and GM-CSFR (required for high-affinity binding and signaling). |
Biochemical characterization, receptor reconstitution studies |
International archives of allergy and immunology |
Medium |
7950399
|
| 1995 |
IL-5 activates the JAK2–STAT1 signaling pathway in human eosinophils: JAK2 is tyrosine-phosphorylated within 1–3 min of IL-5 stimulation, physically associates (co-precipitates) with the β subunit of the IL-5 receptor, and STAT1 (p91) is subsequently tyrosine-phosphorylated and translocates to the nucleus to bind the gamma-activating sequence. |
Immunoprecipitation, immunoblotting for tyrosine phosphorylation, JAK2 autophosphorylation assay, co-IP of JAK2 with IL-5Rβ, EMSA with anti-STAT1 supershift |
Journal of immunology |
High |
7602114
|
| 1995 |
IgE-dependent activation of human lung mast cells (via FcεRI crosslinking) induces IL-5 mRNA expression within 2 h (persisting 48–72 h) and release of immunoreactive IL-5 protein (~731 pg/10^6 cells over 48 h), identifying mast cells as a non-T-cell source of IL-5. |
RT-PCR, in situ hybridization, double in situ hybridization-immunocytochemistry, ELISA; purified mast cells (>93% purity) challenged with anti-IgE |
Journal of immunology |
High |
7543533
|
| 1996 |
Schistosome egg-induced IL-5 is required to recruit eosinophils to the peritoneum, and these recruited eosinophils are themselves a direct source of early IL-4 production (shown by immunocytochemistry), linking IL-5 to downstream IL-4-driven Th2 responses. |
Cytokine/mast cell-deficient mouse models (IL-4-/-, IL-5-/-, mast cell-deficient), immunocytochemical detection of IL-4 in eosinophils, cytokine measurement in peritoneal exudate |
The Journal of experimental medicine |
High |
8920874
|
| 1997 |
IL-5 inhibits eosinophil apoptosis by upregulating Bcl-2 protein and mRNA expression; antisense oligonucleotide against Bcl-2 blocks the IL-5-mediated eosinophil survival effect, demonstrating that Bcl-2 upregulation is the mechanism of IL-5-promoted eosinophil survival. |
In vitro eosinophil culture with rIL-5, apoptosis assay, immunoblot and RT-PCR for Bcl-2, antisense oligonucleotide inhibition |
Clinical and experimental immunology |
High |
9010276
|
| 1997 |
The transcription factor GATA-3 is sufficient to drive IL-5 gene expression in T cells and is required for IL-5 promoter activation; GATA-3 binds with high affinity to an inverted GATA repeat in the IL-5 promoter. By contrast, GATA-3 is not sufficient to drive IL-4 gene expression, revealing differential regulation of these two Th2 cytokine genes. |
Ectopic GATA-3 expression in T cells, antisense GATA-3 RNA in Th2 cells, IL-5 promoter-reporter assay, electrophoretic mobility shift assay (EMSA) for GATA-3 binding to IL-5 promoter |
Journal of immunology |
High |
9780145
|
| 1997 |
The cytokine IL-5 possesses a functional nuclear localization signal and co-transports the extracellular domains of both its α and β receptor subunits to the nucleus in vitro via a 'piggy-back' mechanism, suggesting a nuclear signaling role for IL-5. |
Baculovirus expression of receptor extracellular domains, fluorescent labeling, in vitro nuclear import assay |
FEBS letters |
Medium |
9237664
|
| 1998 |
IL-5 signaling in eosinophils proceeds through two major pathways downstream of its heterodimeric receptor (α-specific, β-common): (1) Lyn → Syk → JAK2 → Ras-MAPK/ERK pathway and (2) JAK-STAT pathway. Lyn, Syk, JAK2, and SHP-2 promote eosinophil survival; Raf-1 (but not Lyn or JAK2) is critical for eosinophil degranulation and adhesion molecule expression. Btk is involved in IL-5-stimulated B cell function but not eosinophil function. |
Immunoprecipitation, kinase assays, pharmacological inhibitors, functional assays (survival, degranulation, adhesion) in human eosinophils |
The American journal of physiology |
High |
9730944
|
| 1998 |
High-affinity binding of IL-5 to its receptor induces receptor oligomerization, tyrosine kinase activation (primarily JAK2), receptor phosphorylation, and recruitment of SH2/PTB domain-containing adaptor proteins; a phosphotyrosine-independent signaling motif in the cytoplasmic domain of βc mediates survival and differentiation signals. |
Receptor reconstitution, mutagenesis of βc, phosphorylation and co-immunoprecipitation assays |
Stem cells |
Medium |
9766809
|
| 1999 |
IL-5 increases expression of FLAP (5-lipoxygenase-activating protein) in human blood eosinophils (by ~51% at protein level) and translocates 5-lipoxygenase to the nucleus, thereby enhancing cysteinyl-leukotriene C4 synthesis ~4-fold; these effects are blocked by cycloheximide and actinomycin D, indicating new gene expression is required. |
Immunostaining for FLAP and 5-LO, immunoblotting, leukotriene C4 synthesis assay, immunofluorescence microscopy, cycloheximide/actinomycin D inhibition |
Journal of immunology |
High |
10384149
|
| 1999 |
p38 MAP kinase selectively regulates IL-5 synthesis in human Th cells: the p38 inhibitor SB203580 dose-dependently suppresses IL-5 production without affecting IL-2, IL-4, or IFN-γ production or T-cell proliferation. |
p38 MAP kinase inhibitor (SB203580) treatment of allergen-specific human Th clones, cytokine ELISA, [3H]thymidine proliferation assay |
Journal of immunology |
Medium |
10528175
|
| 1999 |
IL-2 specifically induces IL-5 mRNA expression (peaking at 24 h) in PBMC from onchocerciasis patients; this induction is abolished by neutralizing anti-IL-2 antibodies. IL-2 does not induce IL-4, IFN-γ, IL-10, or GM-CSF mRNA, and the primary source of IL-5 mRNA is CD4+ T cells. |
RT-PCR for cytokine mRNA, anti-IL-2 neutralizing antibody blocking, CD4+ T cell identification |
Journal of immunology |
Medium |
8099937
|
| 2000 |
IL-5 upregulates cysteinyl leukotriene 1 receptor (CysLT1R) mRNA (2–15-fold within 2–4 h) and protein on eosinophil-differentiated HL-60 cells, resulting in enhanced LTD4-induced Ca2+ mobilization and chemotaxis; this effect requires eosinophil differentiation and is absent in undifferentiated HL-60 cells. |
Northern/RT-PCR for CysLT1R mRNA, flow cytometry for surface protein, Ca2+ flux assay, chemotaxis assay |
Journal of immunology |
Medium |
11046055
|
| 2000 |
Activated mutants of the βc (common β) subunit reveal that IL-5R activation can occur via multiple states differing in receptor stoichiometry; JAK2 activation is the initiating signaling event, and βc dimerization serves as a receptor trigger; β subunit tyrosine phosphorylation generates proliferative and survival signals. |
Site-directed mutagenesis, activated βc mutant isolation, functional assays in cell lines and primary cells, receptor phosphorylation analysis |
Experimental hematology |
Medium |
10720688
|
| 2001 |
IL-5 is necessary and sufficient for eosinophil trafficking to the esophagus: IL-5-transgenic mice (T cell- or enterocyte-driven) show markedly elevated esophageal eosinophils, pharmacological IL-5 administration induces esophageal eosinophilia, and IL-5-deficient mice are resistant to allergen-induced eosinophilic esophagitis. IL-5-driven esophageal eosinophilia is eotaxin-dependent in part. |
IL-5-transgenic mice, IL-5 knockout mice, miniosmotic pump IL-5 delivery, allergen challenge model, genetic cross with eotaxin-deficient mice, histological quantification |
Journal of immunology |
High |
11859139
|
| 2001 |
IL-5 deficiency leads to decreased titers of atheroprotective T15/EO6 natural IgM (anti-phosphorylcholine) and accelerated atherosclerosis; IL-5 provides non-cognate stimulation to innate B-1 cells to secrete T15/EO6 IgM, linking adaptive Th2 IL-5 production to innate B-1 cell antibody output. |
Bone marrow transplant model, IL-5-deficient mice, antibody titer measurement, atherosclerosis quantification |
The Journal of clinical investigation |
High |
15286809
|
| 2001 |
IL-5 overexpression mediates ectopic bone formation in the spleen (ossification) and perturbs skeletal bone metabolism through mobilization of marrow-derived osteogenic progenitors; this effect is transferable by adoptive engraftment of transgenic marrow. |
IL-5-transgenic mouse (NJ.1638), histology (osteoid/osteocyte characterization), morphometric assessment, bone marrow adoptive transfer to wild-type recipients |
The Journal of clinical investigation |
Medium |
11306598
|
| 2002 |
The IL-5 receptor α (IL-5Rα) is selectively expressed on bronchial smooth muscle (but not on saphenous vein or jejunum smooth muscle), and IL-5 directly primes human bronchus for hyperresponsiveness to acetylcholine (17–20-fold reduction in EC50) independent of eosinophils; this effect is blocked by anti-IL-5 and anti-IL-5Rα antibodies. |
Human bronchus organ bath contractility assay, RT-PCR for IL-5Rα and CCR3, antibody neutralization |
The Journal of allergy and clinical immunology |
High |
11897983
|
| 2002 |
IL-13-induced airway eosinophilia (throughout the lung parenchyma) is IL-5-dependent: IL-5 KO mice show markedly attenuated lung eosinophilia in response to intranasal IL-13, while IL-5-transgenic mice show greatly amplified eosinophilia. IL-13-induced mucus production is not affected by IL-5 or eotaxin, dissociating mucus secretion mechanistically from eosinophilia. |
IL-5 KO mice, IL-5 transgenic mice, eotaxin KO mice, double-deficient mice, recombinant murine IL-13 intranasal delivery, histological quantification of BAL and tissue eosinophils, mucus staining |
The Journal of allergy and clinical immunology |
High |
11590387
|
| 2002 |
Pulmonary IL-5 expression induces airway mucus production through a CD4+ T cell-dependent, IL-4Rα-mediated pathway; mucus accumulation in IL-5-transgenic mice is abolished by deficiency of CD4+ cells, αβ TCR+ cells, or anti-IL-4Rα treatment, even though eosinophilia and IL-5 levels remain elevated. |
IL-5-transgenic mice crossed with CD4-/- and αβTCR-/- knockout mice, anti-IL-4Rα antagonist treatment, mucus quantification |
American journal of physiology. Lung cellular and molecular physiology |
High |
11943672
|
| 2002 |
Bcl6 binds to a specific sequence (IL5BS) in the 3'-UTR of the murine and human IL-5 genes and acts as a transcriptional repressor; Bcl6-deficient mice overproduce IL-5 specifically among Th2 cytokines, and mutation of the IL5BS abolishes Bcl6-mediated repression in reporter assays. |
Gel retardation assay, chromatin immunoprecipitation (ChIP), reporter gene assays with wild-type and mutant IL5BS, Bcl6-deficient and lck-Bcl6-transgenic mice |
Journal of immunology |
High |
12097386
|
| 2006 |
IL-5 augments liver fibrosis in Schistosoma mansoni infection by regulating IL-13 activity: IL-5 KO mice show >40% reduction in hepatic fibrosis and loss of alternative macrophage activation markers (arginase-1, Fizz-1, YM-1) despite similar IL-13 production. Granuloma eosinophils are themselves a significant source of IL-13, revealing both direct (eosinophil IL-13 production) and indirect (Th2 polarization) roles for IL-5 in fibrosis. |
IL-5 knockout mice, S. mansoni infection model, histomorphometric fibrosis quantification, gene expression analysis (arginase-1, Fizz-1, YM-1), cytokine measurement |
Infection and immunity |
High |
16495517
|
| 2007 |
In IL-5-transgenic mice with greatly expanded circulating eosinophils, MCA-induced fibrosarcoma incidence and growth are significantly attenuated; histology shows massive eosinophil infiltration in tumors; anti-IL-5Rα and anti-asialo GM1 antibodies reverse the protective effect, implicating eosinophils (and NK cells) as effectors; eosinophils directly kill MCA-induced fibrosarcoma cells in vitro. |
IL-5-transgenic mice, eotaxin-1-deficient mice, eosinophil-deficient strains (IL-5/CCL11-/-, DeltadblGATA), carcinogen-induced tumor model, antibody depletion, in vitro cytotoxicity assay |
Journal of immunology |
High |
17371978
|
| 2007 |
JAK kinase activity is required for ubiquitination of the βc cytoplasmic domain (at lysine residues K566 and K603) and subsequent proteasomal degradation but only partially required for IL-5R internalization; ubiquitination begins at the plasma membrane, increases after internalization, and proteasomal degradation of βc occurs after internalization, followed by terminal lysosomal degradation. |
Flow cytometry, biochemical ubiquitination assays, site-directed mutagenesis of K566/K603, JAK inhibitor treatment, immunoprecipitation |
Journal of leukocyte biology |
High |
17227823
|
| 2008 |
IL-5Rs internalize via two distinct endocytic pathways — clathrin-dependent and lipid raft-dependent; activated (tyrosine-phosphorylated, ubiquitinated, proteasome-targeted) IL-5Rs partition selectively to the clathrin/non-raft fraction; optimal IL-5-induced signaling requires receptor internalization, as blocking either endocytic pathway inhibits co-immunoprecipitation of key signaling molecules with IL-5R. |
Deconvolution microscopy, co-immunoprecipitation, endocytosis inhibitors, transferrin (clathrin) and cholera toxin-B (lipid raft) markers, biochemical fractionation in TF1 cells and human eosinophils |
Journal of leukocyte biology |
High |
18511572
|
| 2010 |
SATB1 directly represses IL-5 transcription during early human Th2 cell differentiation by binding to the IL-5 promoter; SATB1 knockdown increases IL-5 expression, and this up-regulation is partly counteracted by GATA-3 knockdown, indicating a competitive mechanism between SATB1 and GATA-3 at the IL-5 promoter. |
SATB1 ChIP on IL-5 promoter, RNAi knockdown of SATB1 and GATA3, IL-5 mRNA measurement in differentiating human Th2 cells |
Blood |
High |
20522714
|
| 2011 |
IL-5(+) Th2 cells (a minority ~20% subpopulation of Th2 cells) show greater GATA-3 and H3K4me3 binding to the IL-5 promoter, while IL-5(-) Th2 cells show greater H3K27me3 at the IL-5 promoter, demonstrating that hierarchical, epigenetic regulation governs IL-5 gene accessibility within Th2 subsets. |
Intracellular cytokine staining, ChIP for GATA-3/H3K4me3/H3K27me3 at IL-5 promoter, in vitro serial Th2 differentiation, surface marker phenotyping |
Journal of immunology |
High |
21849680
|
| 2011 |
IL-5Rα expression in activated B cells is regulated by a complex of transcription factors including E12, E47, Sp1, c/EBPβ, and Oct-2; IL-5 signals through JAK-STAT, Btk, and Ras/Raf-ERK pathways in B cells and eosinophils to maintain survival and function. |
Transcription factor binding studies, signaling pathway analyses (cited as part of a comprehensive mechanistic review integrating original research data) |
Proceedings of the Japan Academy. Series B |
Medium |
21986312
|
| 2011 |
PARP-1 is required for STAT-6 protein integrity downstream of IL-4R activation; in PARP-1-/- mice, STAT-6 is degraded by calpain (not proteasomes), leading to reduced GATA-3 and consequently reduced IL-5 mRNA and protein in allergen-stimulated conditions. PARP-1 enzymatic activity (not just its presence) is required for STAT-6 stability. |
PARP-1 knockout mice, allergen-induced asthma model, IL-5 ELISA, STAT-6 and GATA-3 immunoblotting, calpain/proteasome inhibitor experiments, ChIP for GATA-3 at IL-5 promoter, IL-5 replenishment experiments |
Allergy |
High |
21276008
|
| 2011 |
Crystal structure of the βc ectodomain reveals an intertwined homodimer with four fibronectin type-III-like domains per chain; domain 1 of one subunit swaps β-strands with domain 3 of the other. Site-directed mutagenesis identifies the interface between domains 1 and 4 as the functional signaling epitope required for IL-5/IL-3/GM-CSF signaling. |
X-ray crystallography, site-directed mutagenesis |
Vitamins and hormones |
High |
17027509
|
| 2011 |
Crystal structure of IL-5 bound to the extracellular domain of IL-5Rα reveals a wrench-like architecture in which IL-5 contacts all three fibronectin III-like domains of IL-5Rα. Mutagenesis confirms the wrench is likely pre-formed. Structural analysis demonstrates that homodimeric IL-5 can bind only one receptor molecule at a time due to steric constraints, even though two equivalent receptor-binding sites exist. |
X-ray crystallography of IL-5/IL-5Rα ectodomain complex, site-directed mutagenesis |
Structure |
High |
22153509
|
| 2015 |
LZTFL1 (upregulated by all-trans retinoic acid in CD4+ T cells) localizes to the plasma membrane, redistributes to the immunological synapse during T cell activation, and promotes IL-5 production: LZTFL1 knockdown reduces IL-5 levels, while overexpression enhances TCR-mediated NFAT signaling. |
Live-cell imaging, siRNA knockdown, overexpression, NFAT reporter assay, IL-5 ELISA in CD4+ T cells |
Journal of immunology |
Medium |
26700766
|
| 2016 |
IL-33 supports eosinophil homeostasis upstream of IL-5: IL-33 drives expansion of IL-5Rα-expressing eosinophil precursor cells in vitro (an effect not produced by IL-5 itself), and the IL-33-induced expansion of mature eosinophils in vivo requires IL-5 (blocked by anti-IL-5 antibody). ST2 deficiency reduces the hypereosinophilia seen in IL-5-transgenic mice despite similar IL-5 levels, positioning IL-33 upstream of IL-5 in eosinophil lineage commitment. |
IL-33-/- and ST2-/- mice, IL-5 transgenic mice crossed with ST2-/-, IL-5-neutralizing antibody, in vitro bone marrow culture with IL-33 or IL-5, flow cytometry for precursor populations |
Journal of immunology |
High |
27683753
|
| 2019 |
IL-5, but not IL-13 or IL-4, directly induces hyperresponsiveness of human small airway smooth muscle: IL-5 does not induce hyperresponsiveness in isolated human small bronchi or human airway smooth muscle cells, in contrast to IL-13 and IL-4 (negative finding mechanistically informative for IL-5). |
Ex vivo human small bronchi organ bath assay, human airway smooth muscle cell culture, contractility measurements, Ca2+ mobilization, RNA sequencing |
The Journal of allergy and clinical immunology |
High |
31805312
|
| 2019 |
Human airway bronchial epithelial cells (HBEC) express a functional IL-5 receptor that triggers intracellular signaling and changes gene expression upon IL-5 stimulation, identifying a direct non-eosinophil target for IL-5 in the airway. |
IL-5 receptor expression on HBEC, signaling assays, gene expression analysis |
Allergy |
Medium |
32246831
|
| 2019 |
Neutrophils infiltrating mouse and human (pediatric asthma BAL) inflamed lungs express IL-5Rα (CD125), and the IL-5 receptor on neutrophils is capable of signal transduction; IL-5-mediated protection from influenza A virus infection is independent of eosinophils in mice, suggesting neutrophils as an alternative cellular target. |
Flow cytometry for IL-5Rα on neutrophils from mouse lungs and human BAL, IL-5R signal transduction assay, IL-5-deficient mice, influenza infection model |
PloS one |
Medium |
31415658
|
| 2019 |
Mast cell-derived IL-5 is important for maintaining the population of IL-10-producing regulatory B cells (IL-10+ Breg) in peripheral lymphoid tissues, which in turn suppress IL-13-producing ILC2s in oxazolone-induced contact hypersensitivity; this reveals a MC → IL-5 → Breg → ILC2 immunoregulatory axis. |
Mast cell-specific models, IL-5 neutralization, flow cytometric characterization of Breg and ILC2 populations, contact hypersensitivity model in mice |
Science advances |
Medium |
31328158
|
| 2020 |
IL-5 stimulates migration and activation of pancreatic tumor cells through STAT5 signaling via IL-5Rα expressed on tumor cells; IL-5Rα expression increases during pancreatic tumor progression in mice and is detectable in human pancreatic ductal adenocarcinoma (7/7 cases by IHC). |
Mouse pancreatic tumor progression models (Akt1Myr/KRasG12D), immunohistochemistry, STAT5 signaling analysis, cell migration assay |
Cell communication and signaling |
Medium |
32552827
|
| 2022 |
The E3 ubiquitin ligases MARCH2 and MARCH3 associate with IL-5Rα, mediate K27-linked polyubiquitination of IL-5Rα at K379 (MARCH2) and K383 (MARCH3), and target it for lysosomal degradation; double knockout of MARCH2/3 enhances IL-5-induced signaling, increases eosinophil numbers in bone marrow and blood, and aggravates OVA-induced eosinophilic airway inflammation. |
Co-immunoprecipitation, ubiquitination assays with K27-linkage specificity, site-directed mutagenesis (K379/K383), MARCH2/3 knockout mice (single and double), OVA airway inflammation model, IL-5 neutralization in vivo |
Cellular & molecular immunology |
High |
35982175
|
| 2024 |
IL-5 promotes eosinophil-lineage expansion specifically through transit amplification of committed progenitors, but deletion or neutralization of IL-5 does not compromise eosinophil maturation per se; IL-5Rα reporter mice and single-cell proteomics/transcriptomics define the precise stage of IL-5 action in eosinophilopoiesis. |
Single-cell proteomics, single-cell transcriptomics, transgenic IL-5Rα reporter mice, IL-5 deletion/neutralization, cell-surface immunophenotyping across eosinophil maturation stages |
Immunity |
High |
38776917
|