IL10是一種細(xì)胞因子，其主要功能是抑制炎癥和調(diào)節(jié)免疫應(yīng)答。最近的研究表明，IL10在各種疾病的治療中具有潛在的應(yīng)用價(jià)值，如自身免疫疾病、炎癥性腸病、感染、癌癥等。研究人員正在探索使用IL10及其受體的激動(dòng)劑來(lái)治療這些疾病，并且正在開(kāi)發(fā)一些新型的IL10類似物。

Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3. In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators. Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro-inflammatory cytokines including granulocyte-macrophage colony-stimulating factor /GM-CSF, granulocyte colony-stimulating factor/G-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF-alpha. Interferes also with antigen presentation by reducing the expression of MHC-class II and co-stimulatory molecules, thereby inhibiting their ability to induce T cell activation. In addition, controls the inflammatory response of macrophages by reprogramming essential metabolic pathways including mTOR signaling.

1. G protein-coupled receptor 39 exhibits an anti-inflammatory activity by enhancing IL-10 production from macrophages PMID: 30053407
2. our results provide direct evidence that the capacity of NK cells to secrete IL-10 is required to maintain the successful "innate" modulation of DC phenotype in the gravid uterus. PMID: 28526846
3. Restrictive IL-10 induction by an innocuous parainfluenza virus vector ameliorates nasal allergy. PMID: 27555458
4. a regulatory loop in which IL-10 directly restricts CD8(+) T cell activation and function through modification of cell surface glycosylation allowing the establishment of chronic infection. PMID: 29396160
5. genome-wide knockdown of 19 ribosomal proteins resulted in decreased IL-10 and increased TNF-alpha production. PMID: 29657255
6. YB-1 orchestrates onset and resolution of renal inflammation via IL-10 gene regulation. PMID: 28664613
7. this study demonstrates IL-10 production and T cell-suppressive capacity in B cell subsets from atherosclerotic apoE (-/-) mice PMID: 28744806
8. IL-10 Knock out-Endothelial progenitor cell-Exosomes were highly enriched in microRNAs and proteins that promote inflammation and apoptosis and inhibit angiogenesis. PMID: 28471299
9. we showed the IL-10 expression of the pyramidal neurons in CA2 and CA3 subregions, for the first time in the world, after infection with the Mu-3 virus PMID: 28493345
10. These data indicate that CD4(+) follicular regulatory T (Tfr) cells play a multifaceted role in the fine-tuning of the germinal center response and identify IL-10 as an important mediator by which Tfr cells support the germinal center reaction PMID: 29054998
11. Decreased interleukin-10 (IL-10) expression was found in the hippocampus of the stressed mice, while no differences in pro-inflammatory cytokine expression and tryptophan (TRYP), kynurenine (KYN) or 3-hydroxy kynurenine (3-HK) levels were found. PMID: 28789949
12. HBV-specific CD8(+) T cells produce IL-10 upon antigen recognition and that this cytokine enhances CD8(+) T cell survival. PMID: 28483675
13. Novel regulatory T-cells that are induced by B cells and do not express Foxp3 and IL-10 alleviate intestinal inflammation in vivo. PMID: 27581189
14. Results provide evidence that macrophage IL-10 production is regulated by NLRP3 and contributes to the pathophysiology of doxorubicin-induced cardiotoxicity independently of IL-1beta. PMID: 27225830
15. Activation of TLR2, TLR4, and TLR9 induced the production of IL-10 in microglia to a greater extent than activation of TLR3. Combination of TLR3 triggering with the other TLRs, enhanced IL-10 through the modulation of its transcription, via interferon (IFN)-beta, but independently of IL-27. Presence of IFN-gamma in the microenvironment abrogated the modulation of IL-10 by TLR3, whereas that of IL-17 had no effect. PMID: 28617991
16. The absence of IL-10 led to longer illness, more weight loss, more death, and slower viral clearance than in mice that produced IL-10. IL-10 influenced development of disease-causing T cells and entry into the brain of B cells producing antiviral antibody. PMID: 29263262
17. Cytokine-inducing and anti-inflammatory activity of chitosan and its low-molecular derivative. PMID: 29513410
18. TonEBP suppresses M2 phenotype via downregulation of the IL-10 in M1 macrophages. PMID: 27160066
19. Nod2-signaling is essentially involved in the well-balanced innate and adaptive immune responses upon Campylobacter jejuni infection of IL-10(-/-) mice. PMID: 28752081
20. CD8(+) T cell-derived IL-10 does not contribute significantly to the resolution of contact hypersensitivity responses. PMID: 27714845
21. Docosahexaenoic acid activates GPR120 to prevent experimental colitis in IL-10 deficient mice. PMID: 28039475
22. in a Leptospira-infected mouse model, study showed evidence of a possible role of IL-10 on host susceptibility, bacterial clearance and on regulation of cytokine gene expression PMID: 28410507
23. in vivo IL-10 treatment increased fibroblast activation (proliferation, migration, and collagen production), an effect that was both directly and indirectly influenced by macrophage M2 polarization PMID: 28439731
24. Suggest that the IL-17A/IL-10/STAT3 signaling pathway plays a crucial role in the pathogenesis of hepatic fibrosis by suppressing hepatocellular autophagy and that blocking this pathway may provide therapeutic benefits for the treatment of hepatic fibrosis. PMID: 28039485
25. Mechanistic studies suggest a PKC-Syk-mediated signaling pathway, to which IL-10 conversely inhibits, is required for activating macrophage self-targeting, followed by phagocytosis independent of calreticulin Moreover, we identified spleen red pulp to be one specific tissue that provides stimuli constantly activating macrophage phagocytosis albeit lacking in Cd47(-/-) or Sirpalpha(-/-) mice. PMID: 27578867
26. High IL10 expression is associated with lung cancer. PMID: 26956044
27. The activation of STAT3 was much higher in Gal12(-/-) macrophages activated by lipopolysaccharide, which was correlated with higher levels of IL-10. Adipocytes showed higher insulin sensitivity when treated with Gal12(-/-) macrophage-conditioned media than those treated with Gal12(+/+) macrophages. PMID: 26873172
28. this study reveals a key role of IL-10 in controlling cellular metabolism via inhibiting mTORC1, and this metabolic control by IL-10 is critical to control of inflammation. PMID: 28473584
29. IL-10-MSCs offered superior protection against LPS-induced ALI. PMID: 29072959
30. methane-rich saline may activate the PI3K-AKT-GSK-3beta pathway to induce IL-10 expression and produce anti-inflammatory effects via the NF-kappaB and MAPK pathways. The findings provide a new pharmacological strategy for management of inflammatory response after acute liver injury. PMID: 28597201
31. plasma adiponectin and leptin were also decreased in IL 10tm.These findings suggest that frailty observed in this mouse model of chronic inflammation may in part be driven by alterations in fat mass, hormone secretion and energy metabolism PMID: 29267271
32. We believe that current findings derived from human and mouse experiments will promote the development of new drugs and therapies based on IL-10 modulation, which may enhance host immunity and bacterial clearance during infection. However, because IL-10 can play both favorable and unfavorable effects over the host depending on the bacterial infection, it may act as a double edge sword. PMID: 27522641
33. IL-12p35 suppresses lymphocyte proliferation, induces expansion of IL-10-expressing and IL-35-expressing B cells and ameliorates autoimmune uveitis. PMID: 28959012
34. aerobic interval training enhanced the anti-inflammatory indices IL-10/TNF-alpha ratio and IL-15 expression in skeletal muscle in tumor-bearing mice. PMID: 27863332
35. Both IL-6 protein production and transcript levels were downregulated by RA in respiratory tract epithelial cells (LETs) , but upregulated in macrophages (MACs). RA also increased transcript levels of MCP-1, GMCSF, and IL-10 in MACs, but not in LETs. Conversely, when LETs, but not MACs, were exposed to RA PMID: 27940088
36. DnaK was able to induce TGF-beta mRNA in treated macrophages in an IL-10 dependent manner. PMID: 27337694
37. findings suggest that the axis IL-10/claudin-10 is a promising target for the development of therapeutic agents against aggressive melanoma PMID: 29145406
38. IL-10 signaling in CD11c+ cells controls small intestinal immune homeostasis by limiting reactivation of local memory T cells and to protect against Helicobacter hepaticus-induced colitis. PMID: 27027442
39. Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells. PMID: 27185659
40. Cisplatin induces immune-suppressive tolerogenic dendritic cells in TLR agonist-induced inflammatory conditions via abundant IL-10 production, thereby skewing Th cell differentiation towards Th2 and Tr1 cells. This relationship may provide cancer cells with an opportunity to evade the immune system. PMID: 27172902
41. Following vasectomy, IL1alpha, IL1beta, IL1ra, IL10, and TNF-alpha may mediate immune reaction in whole epididymis, whereas IL6 and TGF-beta1 may mediate regionally different immune response primarily in the lower part of epididymis. PMID: 27476761
42. this study shows that progesterone and estradiol inhibit the production of IL-10 by activated B cells PMID: 27317920
43. Il-10 deficient mice express IFN-gamma mRNA and clear Leptospira interrogans from their kidneys more rapidly than normal C57BL/6 mice PMID: 28237664
44. Depletion of Tregs increased adaptive T cell responses and deficiency of IL10 reduced morbidity and conferred enhanced protection against influenza virus. PMID: 28086957
45. Data show that the severity experimental autoimmune encephalomyelitis (EAE) were reduced and the serum IL-10 expression levels were increased in CD226 knockout mice than that in control mice when both received EAE induction. PMID: 26942885
46. this study shows that Influenza A virus-induced release of IL-10 inhibits the anti-microbial activities of invariant natural killer T cells during invasive pneumococcal superinfection PMID: 27220813
47. Data show that two functionally distinct cytokines, interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), significantly potentiate the ability of mesenchymal stem cells (MSCs) to inhibit interleukin-10 (IL-10) production by activated regulatory B cells (Bregs). PMID: 27665290
48. The anti-inflammatory functions of p38 MAPK in macrophages are critically dependent on production of IL-10. PMID: 28877953
49. Pretreating mice with carrageenan once a day before injecting LPS increased the levels of IL-10 by 2.5-fold and reduced TNF-alpha production by 2-fold compared with control. So, kappa/beta-carrageenan alone and in combination with LPS enhanced the cellular activity and mobility of peritoneal macrophages by increasing cell adhesion and migration compared with control. PMID: 28130856
50. results demonstrate that IL-10-producing interstitial macrophages negatively regulate Th2- and Th17-mediated inflammatory responses, helping prevent neutrophilic asthma PMID: 26976823

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Secreted.

IL-10 family

KEGG: mmu:16153

STRING: 10090.ENSMUSP00000016673

UniGene: Mm.874