Affinage

IL10

Interleukin-10 · UniProt P22301

Length
178 aa
Mass
20.5 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-10 is a secreted homodimeric cytokine that functions as a central restraint on inflammation, suppressing antigen-presenting cell maturation and proinflammatory cytokine output while promoting tissue-protective immune programs (PMID:11254683, PMID:11160331). Structurally it is an intercalated homodimer of four-helix-bundle protomers that engages a heterodimeric receptor (IL-10R1/IL-10R2), with defined binding sites I and II on the cytokine and receptor (PMID:20846897). Receptor engagement activates JAK-STAT signaling, predominantly STAT3, and induces SOCS family members (SOCS2/SOCS3) that dampen IFN-driven STAT1 signaling (PMID:11034314); STAT3 phosphorylation is the essential output, since loss of IL-10RB abolishes STAT3 activation, fails to suppress LPS-induced cytokines, and impairs bacterial killing through PGE2 overproduction (PMID:31819956). The anti-inflammatory transcriptional program operates partly through chromatin-level repression: IL-10 recruits HDAC3 to deacetylate histones at the Il12b promoter, terminating sustained proinflammatory transcription (PMID:22786766), and in adipocytes IL-10 receptor signaling remodels chromatin accessibility to displace ATF and C/EBPbeta from thermogenic enhancers (PMID:29249357). IL-10 also reprograms macrophages toward an M2 phenotype that supports tissue repair (PMID:22933625), and restrains chronic inflammation metabolically by sustaining mono-unsaturated fatty acid flux to prevent REL-dependent very-long-chain ceramide accumulation (PMID:38383790). IL-10 transcription in T cells is directly driven by c-Maf binding a MARE element in the IL10 promoter (PMID:19414776) and is gated stochastically by chromatin acetylation and TCR signal strength (PMID:17015721). Diverse upstream inputs converge on IL-10 induction, including beta2-adrenergic receptor signaling (PMID:30195028), a PKM2-glycolytic-ATP-to-adenosine/A2aR axis (PMID:39772395), cholesterol biosynthesis intermediates acting via c-Maf (PMID:30700717), and AHR signaling in NK cells (PMID:24403534).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1990 Medium

    Established IL-10 (CSIF/B-TCGF) as a defined cytokine with distinct functional epitopes, separating its co-stimulatory and cytokine-synthesis-inhibiting activities.

    Evidence Neutralizing mAb inhibition and recombinant protein thymocyte proliferation assays

    PMID:2124236

    Open questions at the time
    • Receptor and signaling mechanism not yet defined
    • Epitope mapping not structurally resolved at this stage
  2. 2000 Medium

    Linked IL-10 to the JAK-STAT axis by showing it selectively activates STAT3 and induces SOCS proteins that suppress IFN-driven STAT1 signaling, defining its anti-inflammatory signaling output.

    Evidence In vivo IL-10 injection, RT-PCR, and reporter assays with SOCS overexpression in hepatic cells

    PMID:11034314

    Open questions at the time
    • Direct receptor-JAK coupling not assayed
    • STAT3 versus STAT1 balance under priming not addressed
  3. 2001 Medium

    Demonstrated that IL-10 acts as an autocrine brake on dendritic cell maturation and that endogenous IL-10 suppresses prostaglandin production indirectly by limiting proinflammatory cytokines.

    Evidence Neutralizing antibody DC cultures and IL-10 knockout macrophages with cytokine neutralization epistasis

    PMID:11160331 PMID:11254683

    Open questions at the time
    • Molecular mediators downstream of STAT3 not identified
    • Direct versus indirect COX-2 regulation only inferred from epistasis
  4. 2003 Medium

    Revealed that IFN-gamma priming reprograms IL-10 responses by shifting STAT activation from STAT3 to STAT1, converting an anti-inflammatory program to a proinflammatory one.

    Evidence Gene expression profiling and STAT phosphorylation Western blot in macrophages

    PMID:14607900

    Open questions at the time
    • Mechanism of STAT selection not resolved
    • Receptor-level basis of the switch unknown
  5. 2006 Medium

    Showed IL-10 signaling is actively modulated at the receptor by PKCbeta-driven IL-10R internalization, identifying a route by which pathogen contact silences IL-10 responses.

    Evidence Receptor internalization assays with PKC inhibitors in TLR2-deficient cells

    PMID:16585572

    Open questions at the time
    • Structural basis of internalization not defined
    • Physiological scope beyond zymosan untested
  6. 2009 High

    Identified c-Maf as the direct transcriptional driver of IL-10 via MARE-element binding in the promoter, defining the master regulator of IL-10 transcription in T cells.

    Evidence ChIP promoter binding, retroviral gain-of-function, reporter assays, multiple STAT knockouts

    PMID:19414776

    Open questions at the time
    • Cofactors at the MARE element not enumerated
    • Cell-type-specific differences in c-Maf dependence not fully mapped
  7. 2010 High

    Resolved IL-10 as an intercalated four-helix-bundle homodimer engaging IL-10R1/IL-10R2 at defined sites, providing the structural framework for receptor assembly.

    Evidence Crystal structures of IL-10 and IL-10/sIL-10R1 complexes

    PMID:20846897

    Open questions at the time
    • Full ternary signaling complex with IL-10R2 not captured here
    • JAK recruitment geometry not addressed
  8. 2011 Medium

    Established that IL-10 transcription is epigenetically gated, with monoallelic stochastic expression controlled by chromatin acetylation and TCR signal strength, and repressible by IL-23-driven promoter inaccessibility.

    Evidence Dual-allele reporter mice, ChIP and promoter accessibility assays, cytokine blockade

    PMID:17015721 PMID:22158873

    Open questions at the time
    • Chromatin-modifying enzymes at the IL10 locus not fully identified
    • Quantitative relationship between TCR strength and acetylation incomplete
  9. 2012 High

    Defined a chromatin-level effector mechanism: IL-10 represses sustained Il12b transcription by recruiting HDAC3 to deacetylate the promoter, and promotes M1-to-M2 macrophage switching in tissue repair.

    Evidence ChIP for acetylated H4, HDAC3 shRNA and inhibitors in IL-10 KO macrophages; IL-10 KO mice with macrophage-myoblast coculture

    PMID:22786766 PMID:22933625

    Open questions at the time
    • Link from STAT3 to HDAC3 recruitment not mapped
    • Genes beyond Il12b under HDAC3 control not catalogued
  10. 2015 High

    Showed IL-10 receptor signaling sustains its own producers (Tr1 cells) via p38 MAPK and drives non-canonical ERK/STAT3 effects in neural progenitors, broadening IL-10 outputs beyond canonical STAT3.

    Evidence Reporter and impaired-IL-10R transgenic mice with human Tr1 validation; MEK/ERK inhibitor and lentiviral STAT3 shRNA in SVZ progenitors

    PMID:25762897 PMID:28003377

    Open questions at the time
    • Receptor-to-p38 coupling mechanism not defined
    • Tissue specificity of ERK versus STAT3 outputs unresolved
  11. 2017 High

    Extended IL-10 function to metabolic tissue by demonstrating it represses adipocyte thermogenic transcription through chromatin remodeling and transcription factor displacement.

    Evidence ATAC-seq, ChIP-seq, RNA-seq, and bone marrow transplantation in adipocytes

    PMID:29249357

    Open questions at the time
    • STAT3-to-chromatin-remodeling connection in adipocytes not mechanistically linked
    • Enzymatic basis of accessibility change not identified
  12. 2020 High

    Provided isogenic genetic proof that IL-10RB-STAT3 signaling controls macrophage bacterial killing by restraining PGE2 overproduction, unifying the anti-inflammatory and antimicrobial roles.

    Evidence iPSC-derived IL10RB-/- macrophages with gene-correction rescue, STAT3 Western blot, bacterial killing and PGE2 inhibition

    PMID:31819956

    Open questions at the time
    • STAT3 target genes controlling PGE2 synthesis not enumerated
    • Generalizability across pathogens beyond Salmonella untested
  13. 2024 High

    Defined a metabolic axis of IL-10 anti-inflammatory action: IL-10 sustains MUFA flux to prevent REL-dependent very-long-chain ceramide accumulation, with CERS2 as the key node.

    Evidence Cers2/IL-10 double genetic deletion, metabolic flux analysis, MUFA rescue in vitro and in vivo

    PMID:38383790

    Open questions at the time
    • How IL-10 signaling controls MUFA synthesis flux mechanistically unresolved
    • Connection between ceramides and REL activation not fully detailed
  14. 2025 Medium

    Identified a glycolytic-metabolic input to IL-10 induction, where tetrameric PKM2 raises ATP release that is converted to adenosine to activate A2aR and drive IL-10 production.

    Evidence PKM2 activator TEPP-46, PKM2-deficient macrophages, ectonucleotidase and A2aR pharmacology

    PMID:39772395

    Open questions at the time
    • Transcriptional link from A2aR to the IL10 locus not defined
    • Relative contribution among the many upstream IL-10 inducers unquantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the canonical STAT3 signal is mechanistically translated into the diverse chromatin-remodeling, metabolic, and HDAC3-dependent effector programs across cell types remains unresolved.
  • No unified map from receptor engagement to cell-type-specific transcriptional outcomes
  • Integration of the multiple upstream inducers into a single regulatory logic is incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 3
Partners
IL10RAIL10RB

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 IL-10 (identified as identical to CSIF/B-TCGF) acts as a co-stimulatory growth factor for mature and immature thymocytes in the presence of IL-2 and IL-4, and IL-10 is secreted by fetal thymocytes, adult thymocytes, and splenocytes upon TCR stimulation. EBV gene BCRF1 shares CSIF activity but lacks thymocyte-stimulating activity, indicating at least two functional epitopes on IL-10. Neutralizing mAb inhibition, recombinant protein activity assay, thymocyte proliferation assay Journal of immunology Medium 2124236
1992 Murine keratinocytes produce IL-10 mRNA and protein in response to hapten application, with peak expression at 12 hours; depletion of Langerhans cells, dendritic epidermal cells, and T lymphocytes confirmed keratinocytes as the main source. Quantitative RT-PCR, immunoprecipitation with IL-10 mAb, cell depletion experiments Journal of immunology Medium 1607665
2000 IL-10 injection into mice activates STAT3 but not STAT1 in the liver, and induces SOCS2, SOCS3, and CIS mRNA expression. Overexpression of SOCS2 or SOCS3 inhibited IFN-alpha-induced reporter activity in hepatic cells, indicating that IL-10 suppresses IFN-alpha-activated STAT1 signaling at least partly by inducing SOCS2 and SOCS3. In vivo IL-10 injection, RT-PCR, reporter gene assay, overexpression in hepatic cells FEBS letters Medium 11034314
2000 In reperfused ischemic myocardium, CD5+ lymphocytes are the predominant source of IL-10; IL-10 induces TIMP-1 mRNA expression in isolated mononuclear cells, and this effect is blocked by a neutralizing antibody to IL-10, suggesting IL-10 promotes cardiac healing by modulating mononuclear cell phenotype and inducing TIMP-1. In vitro neutralizing antibody blockade, RT-PCR, mononuclear cell culture with cardiac lymph Journal of immunology Medium 10946312
2001 Autocrine IL-10 prevents spontaneous maturation of monocyte-derived dendritic cells in vitro and limits LPS- and CD40L-mediated maturation. Neutralization of IL-10 in DCs enhances surface CD83, CD80, CD86, and MHC expression, increases TNF-alpha and IL-12 release, and augments T cell activation and Th1 polarization. IL-10R1 expression is regulated by both transcriptional and posttranscriptional mechanisms in DCs. Neutralizing antibody addition to DC cultures, flow cytometry, cytokine ELISA, mRNA analysis Journal of immunology Medium 11254683
2001 IL-10 synergizes with LPS and IFN-gamma to increase S100A8 mRNA (>9-fold) and secreted protein (~4-fold) in macrophages. This synergy requires de novo protein synthesis, is mediated by increased transcription (mapped to a 178-bp promoter fragment), and involves MAP kinase/COX-2/cAMP pathways, mechanistically distinct from STAT pathway-mediated IL-10 gene regulation. mRNA stability assay, luciferase reporter/transfection, blocking experiments, RT-PCR, ELISA Journal of immunology Medium 11342660
2001 IL-10 deficiency leads to exaggerated COX-2 mRNA and protein induction and 5.6-fold greater PGE2 production in response to LPS compared to wild-type mice. Neutralization of IFN-gamma, TNF-alpha, or IL-12 markedly decreased COX-2 induction in IL-10-deficient cells, indicating that endogenous IL-10 suppresses PG production indirectly by limiting proinflammatory cytokine production. IL-10 knockout mice, RT-PCR, Western blot, cytokine neutralization in culture Journal of immunology Medium 11160331
2003 IFN-gamma preactivation of macrophages does not suppress IL-10-induced JAK-STAT signaling (STAT3 activation is preserved) but switches the balance of IL-10 STAT activation from STAT3 to STAT1, reprogramming macrophage responses to IL-10 and converting its anti-inflammatory gene expression program to a proinflammatory one. Gene expression profiling, Western blot for STAT phosphorylation, macrophage cytokine production assays Journal of immunology Medium 14607900
2004 IL-10 reduces FcepsilonRI beta subunit protein expression in mouse bone marrow-derived mast cells without altering alpha or gamma subunits, thereby diminishing IgE-mediated FcepsilonRI upregulation and inflammatory cytokine production. IL-10 augments the inhibitory effect of IL-4 on FcepsilonRI expression. Western blot, flow cytometry, mast cell culture with cytokine treatment Journal of immunology Medium 14978125
2006 Zymosan-induced inhibition of IL-10 signaling in macrophages involves protein kinase Cbeta and internalization of the IL-10 receptor (IL-10R), independently of TLR2 and phagocytosis, and requires direct contact with zymosan. IL-10 signaling assays, receptor internalization experiments, pharmacological inhibitors, TLR2-deficient cells Journal of immunology Medium 16585572
2006 PGE2 selectively augments IL-10-induced STAT3 and STAT1 phosphorylation and SOCS3 gene expression in THP-1 cells via EP2 or EP4 receptors, cAMP elevation, and requires de novo gene expression; this effect is mediated through protein kinase A and PI3K pathways. Western blot for STAT phosphorylation, real-time PCR, pharmacological agonists/antagonists, signaling inhibitors Journal of immunology Medium 16818766
2006 IL-10 is predominantly monoallelically expressed in CD4+ T cells via a stochastic regulation mechanism; the probability of allelic transcription depends on the strength of TCR signaling and the ability to overcome chromatin hypoacetylation. In vivo Ag-experienced T cells have a higher basal probability to transcribe IL-10 compared with naive cells. IL-10 reporter mouse (dual allele), allelic expression analysis, in vivo antigen experience experiments Journal of immunology Medium 17015721
2009 The transcription factor c-Maf is upregulated by IL-6 plus TGF-beta in Th17 cells in a STAT3-dependent manner, and c-Maf directly transactivates IL-10 gene expression by binding to a MARE (Maf recognition element) motif in the IL-10 promoter. Retroviral transduction of c-Maf induces IL-10 expression in STAT6-deficient T cells. Gene array, retroviral transduction, ChIP (promoter binding), reporter assay, STAT3/STAT6/STAT1 knockout analysis Journal of immunology High 19414776
2010 IL-10 is a structurally intercalated homodimer with each protomer containing a classical four-helix bundle; it signals by binding to two receptor chains (IL-10R1 and IL-10R2). Structural analysis of the binary IL-10/sIL-10R1 complex defines receptor binding site I on IL-10R1, with receptor binding site II on helices A and F of IL-10. Crystal structure analysis of IL-10 and its receptor complexes Cytokine & growth factor reviews High 20846897
2011 IL-23 overexpression in the intestinal mucosa suppresses IL-10 gene transcription in CD4+ T cells; IL-23 reduces histone accessibility at the IL-10 promoter (measured by chromatin immunoprecipitation and promoter accessibility assay), and blocking IL-23 restores IL-10 production by lamina propria mononuclear cells. ChIP assay, promoter accessibility assay, cytokine blockade, in vitro polarization of Th2 cells Journal of biological chemistry Medium 22158873
2012 IL-10 regulates the switch of muscle macrophages from M1 to M2 phenotype in injured muscle in vivo; ablation of IL-10 amplifies the Th1 response and prevents increases in CD163 and arginase-1. In vitro, M2 macrophages activated by IL-10 increase myoblast proliferation without affecting MyoD or myogenin, whereas direct IL-10 stimulation of muscle cells has no effect on proliferation or these markers. IL-10 KO mice, in vitro coculture of macrophages and myoblasts, gene expression analysis Journal of immunology Medium 22933625
2012 IL-10 inhibits sustained Il12b (IL-12 p40) expression in macrophages through HDAC3-mediated histone deacetylation at the Il12b promoter. In IL-10-deficient macrophages, acetylated histone H4 association with the Il12b promoter is prolonged; HDAC inhibitors and HDAC3 shRNA confirmed involvement of HDAC3, while there were no differences in NF-kappaB, MAPK, mRNA stability, or nucleosome remodeling. ChIP for acetylated histone H4, HDAC inhibitors, HDAC3 shRNA knockdown, RT-PCR, Western blot in IL-10 KO macrophages Journal of immunology High 22786766
2013 Eosinophil-derived IL-10 at initiation of Trichinella spiralis infection expands IL-10+ myeloid dendritic cells and CD4+ IL-10+ T lymphocytes that inhibit inducible NO synthase (iNOS) expression, protecting intracellular larvae from NO-mediated killing. IL-10 reporter cells, cell depletion/adoptive transfer, iNOS expression analysis, eosinophil-specific studies Journal of immunology Medium 25210122
2014 NK cells require both IL-12 signaling and activation of the aryl hydrocarbon receptor (AHR) for optimal IL-10 production during Toxoplasma gondii infection. IL-12 stimulation increases NK cell AHR levels; AHR and ARNT (AHR nuclear translocator) are required for optimal IL-10 production, as shown by impaired IL-10 expression in Ahr-/- NK cells. IL-10 reporter mouse, IL-12 depletion, Ahr-/- knockout mice, in vitro stimulation assays Journal of immunology Medium 24403534
2015 In Tr1 (regulatory T) cells, IL-10 receptor signaling activates p38 MAPK, which sustains IL-10 production and is required for TR1 cell suppressive activity in vivo. TR1 cells with impaired IL-10 receptor signaling lose their regulatory activity in a murine IBD model, confirmed with human TR1 cells. Double reporter mice (IL-10eGFP/Foxp3mRFP), transgenic mice with impaired IL-10R signaling, in vitro p38 MAPK analysis, human TR1 cell validation Journal of immunology High 28003377
2015 In adult SVZ neural progenitors, IL-10 targets Nestin+ progenitors and activates phosphorylation of both ERK and STAT3. Inhibition of MEK/ERK restores neurogenesis to normal levels; silencing STAT3 with lentiviral vectors impairs neurogenesis by blocking IL-10 effects, identifying ERK and STAT3 as downstream effectors of IL-10 in adult neurogenesis. In vitro and in vivo IL-10 treatment, MEK/ERK inhibitor, lentiviral STAT3 shRNA, phospho-ERK and phospho-STAT3 Western blot Frontiers in cellular neuroscience Medium 25762897
2016 B1a (CD19+CD11b+CD5+) regulatory B cells rapidly express IL-10 in a TLR2-dependent manner in response to S. aureus; adoptive transfer of B1a cells is protective during acute systemic S. aureus infection in IL-10-deficient hosts, demonstrating that B1a-cell-derived IL-10 is the protective mediator. Flow cytometry, TLR2-dependence analysis, adoptive cell transfer, IL-10-deficient mice Journal of immunology Medium 28167629
2017 IL-10 signaling in adipocytes (via IL-10 receptor alpha, which is highly enriched in mature adipocytes and induced by differentiation, obesity, and aging) represses thermogenic gene transcription by altering chromatin accessibility and inhibiting ATF and C/EBPbeta recruitment to key enhancer regions. ATAC-seq, ChIP-seq, RNA-seq, bone marrow transplantation to define IL-10 source, adipocyte-specific functional assays Cell High 29249357
2018 Norepinephrine (NE) blocks proinflammatory cytokine secretion exclusively through the beta2-adrenergic receptor (ADRB2) by rapidly inducing IL-10 secretion from innate cells in response to TLR signals; Adrb2-/- animals show elevated TNF-alpha and reduced IL-10 during endotoxemia, and LPS-mediated lethality in Adrb2-/- mice is rescued by exogenous IL-10. ADRB2 knockout mice, IL-10 rescue experiment, infection models, cytokine ELISA, beta2-specific agonist administration Brain, behavior, and immunity Medium 30195028
2019 The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells; inhibition with atorvastatin or 25-hydroxycholesterol specifically blocks switching to IL-10+ phenotype. Mechanistically, 25-hydroxycholesterol significantly decreases c-Maf, the master transcriptional regulator of IL10 in T cells. Pharmacological inhibition (atorvastatin, 25-hydroxycholesterol), gene expression analysis, pathway analysis of human T cells Nature communications Medium 30700717
2020 Loss of IL-10 signaling (via IL10RB deficiency) in macrophages results in failure to phosphorylate STAT3 in response to IL-10, failure to reduce LPS-induced inflammatory cytokines, and a striking defect in Salmonella killing. IL-10RB-/- macrophages overproduce PGE2, and pharmacological inhibition of PGE2 synthesis or receptor blockade enhances bacterial killing, revealing a regulatory interaction between IL-10 signaling and PGE2 production. iPSC-derived IL10RB-/- macrophages, gene correction rescue, STAT3 phosphorylation Western blot, bacterial killing assay, PGE2 pharmacological inhibition Journal of experimental medicine High 31819956
2022 IL-10 inhibits RANKL-induced osteoclast differentiation by promoting MEG3 methylation (suppressing MEG3 lncRNA expression). MEG3 binds STAT1 and prevents STAT1 from binding to IRF8, thereby maintaining IRF8 levels that inhibit osteoclastogenesis; knockdown of MEG3 inhibits osteoclast differentiation and alleviates osteolysis. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, dual-luciferase assay, MEG3 knockdown, TRAP staining Cellular signalling Medium 35525407
2024 IL-10 deficiency leads to increased saturated very long chain (VLC) ceramide accumulation due to decreased mono-unsaturated fatty acid (MUFA) synthesis flux; ceramide synthase 2 (CERS2) deletion limits the exacerbated inflammatory gene expression of IL-10 deficiency in vitro and in vivo. The persistent inflammation mediated by VLC ceramides is largely dependent on sustained activity of the transcription factor REL, and restoring MUFA availability limits VLC ceramide production and the associated inflammation. Genetic deletion of Cers2 in IL-10-deficient background, metabolic flux analysis, gene expression profiling, MUFA supplementation rescue, in vitro and in vivo validation Nature High 38383790
2025 Tetrameric PKM2 activation in LPS-stimulated macrophages induces IL-10 production by increasing glycolytic ATP release; extracellular ATP is converted to adenosine by ectonucleotidases, and adenosine activates the A2a receptor (A2aR) to enhance IL-10 production. This effect is abolished in PKM2-deficient macrophages and is associated with improved mitochondrial health. PKM2 pharmacological activator (TEPP-46), PKM2-deficient macrophages, ectonucleotidase pathway analysis, A2aR pharmacology, mitochondrial assays Cell reports Medium 39772395

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 The regulation of IL-10 production by immune cells. Nature reviews. Immunology 2523 20154735
2001 Regulatory activity of autocrine IL-10 on dendritic cell functions. Journal of immunology (Baltimore, Md. : 1950) 426 11254683
2012 IL-10 triggers changes in macrophage phenotype that promote muscle growth and regeneration. Journal of immunology (Baltimore, Md. : 1950) 385 22933625
1990 IL-10, a novel growth cofactor for mature and immature T cells. Journal of immunology (Baltimore, Md. : 1950) 380 2124236
2011 The role of IL-10 in immune regulation during M. tuberculosis infection. Mucosal immunology 370 21451501
2011 IL-10 elicits IFNγ-dependent tumor immune surveillance. Cancer cell 359 22172723
2008 Strategies for use of IL-10 or its antagonists in human disease. Immunological reviews 351 18613832
1992 Identification and induction of keratinocyte-derived IL-10. Journal of immunology (Baltimore, Md. : 1950) 303 1607665
2017 IL-10: A Multifunctional Cytokine in Viral Infections. Journal of immunology research 288 28316998
2019 Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10. Cell 263 30612739
2000 IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury. Journal of immunology (Baltimore, Md. : 1950) 243 10946312
2010 IL-10 family of cytokines. Cytokine & growth factor reviews 239 21112807
2015 Suppression of antigen presentation by IL-10. Current opinion in immunology 237 25597442
2011 IL-10 and IL-10 receptor defects in humans. Annals of the New York Academy of Sciences 207 22236434
2009 c-Maf regulates IL-10 expression during Th17 polarization. Journal of immunology (Baltimore, Md. : 1950) 200 19414776
2003 IL-10, an inflammatory/inhibitory cytokine, but not always. Immunology letters 190 12644313
2007 IL-10, T cell exhaustion and viral persistence. Trends in microbiology 180 17336072
2024 IL-10 constrains sphingolipid metabolism to limit inflammation. Nature 179 38383790
2002 IL-10 regulates murine lupus. Journal of immunology (Baltimore, Md. : 1950) 176 12165544
1992 Functional characterization of human IL-10. International archives of allergy and immunology 174 1336421
2018 The β2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion. Brain, behavior, and immunity 173 30195028
2014 The regulation of IL-10 expression. Current topics in microbiology and immunology 159 25004818
2017 IL-10 Signaling Remodels Adipose Chromatin Architecture to Limit Thermogenesis and Energy Expenditure. Cell 158 29249357
1999 Interleukin-10 (IL-10) genotypes in inflammatory bowel disease. Tissue antigens 148 10551422
2008 Role of IL-10 in the resolution of airway inflammation. Current molecular medicine 139 18691071
2001 Central nervous system expression of IL-10 inhibits autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950) 137 11123343
2008 IL-10 modulates depressive-like behavior. Journal of psychiatric research 121 18394646
2019 The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells. Nature communications 113 30700717
2003 Reprogramming of IL-10 activity and signaling by IFN-gamma. Journal of immunology (Baltimore, Md. : 1950) 111 14607900
2013 Activated platelets enhance IL-10 secretion and reduce TNF-α secretion by monocytes. Journal of immunology (Baltimore, Md. : 1950) 109 24048901
2007 IL-10 controls ultraviolet-induced carcinogenesis in mice. Journal of immunology (Baltimore, Md. : 1950) 105 17579057
2016 IL-10 Receptor Signaling Is Essential for TR1 Cell Function In Vivo. Journal of immunology (Baltimore, Md. : 1950) 97 28003377
2019 The Role of IL-10 in Malaria: A Double Edged Sword. Frontiers in immunology 96 30809232
2002 IL-10 expression profiling in human monocytes. Journal of leukocyte biology 96 12377950
2014 The aryl hydrocarbon receptor promotes IL-10 production by NK cells. Journal of immunology (Baltimore, Md. : 1950) 88 24403534
2019 Il-10 producing T and B cells in allergy. Seminars in immunology 86 31711770
2000 IL-10 attenuates IFN-alpha-activated STAT1 in the liver: involvement of SOCS2 and SOCS3. FEBS letters 85 11034314
2001 Il-10 is a central regulator of cyclooxygenase-2 expression and prostaglandin production. Journal of immunology (Baltimore, Md. : 1950) 80 11160331
2006 Prostaglandin E2 augments IL-10 signaling and function. Journal of immunology (Baltimore, Md. : 1950) 78 16818766
2017 IL-10 Plays Opposing Roles during Staphylococcus aureus Systemic and Localized Infections. Journal of immunology (Baltimore, Md. : 1950) 77 28167629
2013 Role of IL-10 in the progression of kidney disease. World journal of transplantation 77 24392313
2021 IL-10 in glioma. British journal of cancer 73 34349251
2001 Il-10 up-regulates macrophage expression of the S100 protein S100A8. Journal of immunology (Baltimore, Md. : 1950) 71 11342660
2015 IL-10 regulates adult neurogenesis by modulating ERK and STAT3 activity. Frontiers in cellular neuroscience 69 25762897
2002 IL-10 gene therapy prevents TNBS-induced colitis. Gene therapy 69 12457286
1995 IL-10 immunosuppression in transplantation. Current opinion in immunology 66 8573306
2015 IL-10 Indirectly Regulates Corneal Lymphangiogenesis and Resolution of Inflammation via Macrophages. The American journal of pathology 65 26608451
2015 IL-10 mediates plasmacytosis-associated immunodeficiency by inhibiting complement-mediated neutrophil migration. The Journal of allergy and clinical immunology 65 26653800
2016 Opposing roles of IL-10 in acute bacterial infection. Cytokine & growth factor reviews 64 27522641
2012 IL-10 regulates Il12b expression via histone deacetylation: implications for intestinal macrophage homeostasis. Journal of immunology (Baltimore, Md. : 1950) 64 22786766
2020 IL-10 Dampens an IL-17-Mediated Periodontitis-Associated Inflammatory Network. Journal of immunology (Baltimore, Md. : 1950) 61 32169848
2016 IL-10 Modulates Th17 Pathogenicity during Autoimmune Diseases. Journal of clinical & cellular immunology 61 27308096
2014 Eosinophil-derived IL-10 supports chronic nematode infection. Journal of immunology (Baltimore, Md. : 1950) 59 25210122
2010 Structural analysis of cytokines comprising the IL-10 family. Cytokine & growth factor reviews 59 20846897
2021 IL-10 as a Th2 Cytokine: Differences Between Mice and Humans. Journal of immunology (Baltimore, Md. : 1950) 55 34663593
2000 Pregnancy specific glycoprotein 18 induces IL-10 expression in murine macrophages. European journal of immunology 55 10940872
2020 Loss of IL-10 signaling in macrophages limits bacterial killing driven by prostaglandin E2. The Journal of experimental medicine 54 31819956
2014 S100A8 induces IL-10 and protects against acute lung injury. Journal of immunology (Baltimore, Md. : 1950) 54 24532576
2004 IL-10 inhibits Fc epsilon RI expression in mouse mast cells. Journal of immunology (Baltimore, Md. : 1950) 54 14978125
2008 IL-10 and the resolution of infections. The Journal of pathology 53 18161757
2019 Epigenetic and transcriptional mechanisms for the regulation of IL-10. Seminars in immunology 51 31676122
2016 The role of IL-10 in Mycobacterium avium subsp. paratuberculosis infection. Cell communication and signaling : CCS 50 27905994
2013 Macrophage and T cell produced IL-10 promotes viral chronicity. PLoS pathogens 50 24244162
2004 IL-10 gene polymorphisms in infectious disease and SIDS. FEMS immunology and medical microbiology 50 15325397
2022 IL-10 revisited in systemic lupus erythematosus. Frontiers in immunology 49 35979356
2010 IL-10 restricts memory T cell inflation during cytomegalovirus infection. Journal of immunology (Baltimore, Md. : 1950) 49 20713884
2018 Chronic Lymphocytic Leukemia-Derived IL-10 Suppresses Antitumor Immunity. Journal of immunology (Baltimore, Md. : 1950) 47 29712773
2021 IL-10 Dysregulation Underlies Chemokine Insufficiency, Delayed Macrophage Response, and Impaired Healing in Diabetic Wounds. The Journal of investigative dermatology 46 34517005
2019 IL-10 secreting B cells regulate periodontal immune response during periodontitis. Odontology 45 31701299
2011 IL-10 expression is regulated by HPV E2 protein in cervical cancer cells. Molecular medicine reports 45 21468579
2006 Stochastic monoallelic expression of IL-10 in T cells. Journal of immunology (Baltimore, Md. : 1950) 45 17015721
2019 Human-Specific Function of IL-10 in Adipose Tissue Linked to Insulin Resistance. The Journal of clinical endocrinology and metabolism 44 31132124
2000 Mantle cell lymphoma proliferates upon IL-10 in the CD40 system. Leukemia 43 10942246
2011 Interleukin (IL)-23 suppresses IL-10 in inflammatory bowel disease. The Journal of biological chemistry 42 22158873
2011 Uterine Regulatory T cells, IL-10 and hypertension. American journal of reproductive immunology (New York, N.Y. : 1989) 41 21726343
2025 Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine. Cell reports 39 39772395
2022 Microbial metabolite butyrate promotes induction of IL-10+IgM+ plasma cells. PloS one 39 35333906
2017 IL-10 and socs3 Are Predictive Biomarkers of Dengue Hemorrhagic Fever. Mediators of inflammation 39 28827898
2006 Selective regulation of IL-10 signaling and function by zymosan. Journal of immunology (Baltimore, Md. : 1950) 39 16585572
2021 IL-10 Signaling in the Tumor Microenvironment of Ovarian Cancer. Advances in experimental medicine and biology 38 33559854
2019 IL-10 and CXCL2 in trigeminal ganglia in neuropathic pain. Neuroscience letters 37 30904573
2003 IL-10 mediates sigma 1 receptor-dependent suppression of antitumor immunity. Journal of immunology (Baltimore, Md. : 1950) 37 12646621
2015 Macrophage Polarization in IL-10 Treatment of Particle-Induced Inflammation and Osteolysis. The American journal of pathology 36 26597885
2014 IL-10: achieving balance during persistent viral infection. Current topics in microbiology and immunology 36 25004816
2002 IL-10 in myeloma cells. Leukemia & lymphoma 36 12148907
2022 A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis. Acta pharmaceutica Sinica. B 35 35967288
2021 Adiponectin/AdipoR1 Axis Promotes IL-10 Release by Human Regulatory T Cells. Frontiers in immunology 35 34084174
2013 IL-10 modulates serotonin transporter activity and molecular expression in intestinal epithelial cells. Cytokine 35 23410504
2020 IL-27 Counteracts Neuropathic Pain Development Through Induction of IL-10. Frontiers in immunology 34 32047492
2016 Inverse Correlation between IL-10 and HIF-1α in Macrophages Infected with Histoplasma capsulatum. Journal of immunology (Baltimore, Md. : 1950) 34 27271565
2008 Association of IL-10 receptor 2 (IL10RB) SNP with systemic sclerosis. Biochemical and biophysical research communications 34 18588853
2021 Microglial IL-10 and β-endorphin expression mediates gabapentinoids antineuropathic pain. Brain, behavior, and immunity 33 33862171
2004 Differential expression of IL-10 receptor by epithelial cells and alveolar macrophages. Allergy 32 15080831
2021 NK Cell-Derived IL-10 Supports Host Survival during Sepsis. Journal of immunology (Baltimore, Md. : 1950) 29 33514512
2014 Modulation of dendritic cell functions by viral IL-10 encoded by human cytomegalovirus. Frontiers in microbiology 29 25071749
2022 IL-10 inhibits osteoclast differentiation and osteolysis through MEG3/IRF8 pathway. Cellular signalling 28 35525407
2014 IL-10 exacerbates xenogeneic GVHD by inducing massive human T cell expansion. Clinical immunology (Orlando, Fla.) 28 25463432
2018 Ascites IL-10 Promotes Ovarian Cancer Cell Migration. Cancer microenvironment : official journal of the International Cancer Microenvironment Society 27 30039195
2018 Inhaled IL-10 Suppresses Lung Tumorigenesis via Abrogation of Inflammatory Macrophage-Th17 Cell Axis. Journal of immunology (Baltimore, Md. : 1950) 27 30257887
2014 IL-10 deficiency increases renal ischemia-reperfusion injury. Nephron. Experimental nephrology 27 25376659

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