IL-17A是一種促炎癥細(xì)胞因子，可以促進(jìn)炎癥反應(yīng)和免疫細(xì)胞的激活。最新研究表明，IL-17A在多種疾病的發(fā)病機(jī)制中起著重要作用，如自身免疫性疾病、感染性疾病、腫瘤等。近年來，許多針對(duì)IL-17A的治療方法被提出，例如抗IL-17A抗體和抑制IL-17A表達(dá)的藥物等，這些方法在臨床治療中已經(jīng)取得了一些成功。

Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Signals via IL17RA-IL17RC heterodimeric receptor complex, triggering homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation. Plays an important role in connecting T cell-mediated adaptive immunity and acute inflammatory response to destroy extracellular bacteria and fungi. As a signature effector cytokine of T-helper 17 cells (Th17), primarily induces neutrophil activation and recruitment at infection and inflammatory sites. In airway epithelium, mediates neutrophil chemotaxis via induction of CXCL1 and CXCL5 chemokines. In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells. Effector cytokine of a subset of gamma-delta T cells that functions as part of an inflammatory circuit downstream IL1B, TLR2 and IL23A-IL12B to promote neutrophil recruitment for efficient bacterial clearance. Effector cytokine of innate immune cells including invariant natural killer cell (iNKT) and group 3 innate lymphoid cells that mediate initial neutrophilic inflammation. Involved in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Upon acute injury, has a direct role in epithelial barrier formation by regulating OCLN localization and tight junction biogenesis. As part of the mucosal immune response induced by commensal bacteria, enhances host's ability to resist pathogenic bacterial and fungal infections by promoting neutrophil recruitment and antimicrobial peptides release. In synergy with IL17F, mediates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers. Involved in antiviral host defense through various mechanisms. Enhances immunity against West Nile virus by promoting T cell cytotoxicity. May play a beneficial role in influenza A virus (H5N1) infection by enhancing B cell recruitment and immune response in the lung. Contributes to influenza A virus (H1N1) clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense.

1. gammadeltaT17 cells constitutively express chemokine receptors CCR6 and CCR2 PMID: 28580944
2. this paper shows that IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5 PMID: 28612841
3. this study shows that IL-17A negatively regulates lymphangiogenesis in T helper 17 cell-mediated inflammation PMID: 28930285
4. The present study demonstrated that a high fat diet induces IL-17A expression, which exacerbates the progression of nonalcoholic fatty liver disease by inhibiting fatty acid beta-oxidation and promoting the accumulation of triglycerides (TG). PMID: 28153707
5. JunB has an essential role in IL-23-dependent pathogenicity of Th17 cells PMID: 28555647
6. Gamma-delta T cells are a prime source of protumoral IL17A in breast cancer. PMID: 29070614
7. blocking activin/ACVR2A impaired the potency of hepatic stellate cells to produce collagens in response to IL17s. PMID: 29620144
8. this study shows the positive effects of IL-17 on the early-stage differentiation and negative effects on the calcification of primary osteoblasts in vitro PMID: 29438885
9. these data suggest that IL-17A promotes DVT pathogenesis by enhancing platelet activation and aggregation, neutrophil infiltration, and EC activation PMID: 29482157
10. These findings highlight a regulatory pathway of Tiam1/Rac1 in Th17 cells and suggest that it may be a therapeutic target in multiple sclerosis. PMID: 27725632
11. DAPK deficiency leads to excess HIF-1a accumulation, enhanced IL-17 expression and exacerbated experimental autoimmune encephalomyelitis. PMID: 27312851
12. decreased COX-2 and IL-17 levels were observed in both groups treated with Nintedanib in the prostate anterior lobe. Thus, we concluded that Nintedanib was effective in delaying tumor progression and, despite not directly acting on inflammation, Nintedanib may adversely affect inflammatory pathways, favoring prostate cancer delay PMID: 29429524
13. In studies of mouse and human pancreatic tumors and precursors, we found that immune cell-derived IL17 regulated development of tuft cells and stem cell features of pancreatic cancer cells via increased expression of DCLK1, POU2F3, ALDH1A1, and IL17RC. PMID: 29604293
14. The reaction of IL-17A in the acute lung injury induced by LPS is stronger than that by PQ. PMID: 28600744
15. IL17A promoted osteoblast differentiation and calcification in a partly AKT2dependent manner in MC3T3E1 cells in vitro, possibly reflecting compensation by other signaling pathways. The results of the present study may offer novel perspectives to guide the clinical strategy for the prevention and treatment of periodontitis PMID: 28849233
16. Mechanistically, CREB, activated by CD3-PKC- signaling, plays a key role in regulating Th17 cell differentiation, at least in part through directly binding to the Il17-Il17f gene locus. PMID: 29050947
17. Data show that interleukin-17 (IL-17) and fungal candidalysin amplify inflammation in a self-reinforcing feed-forward loop. PMID: 29101209
18. The data indicate that IL-17A contributes to augmented responses to ozone in db/db mice. Furthermore, IL-17A appears to act at least in part by inducing expression of gastrin-releasing peptide receptor. PMID: 28957638
19. miR203 expression may be upregulated by IL17 stimulation, and miR203 is a positive regulator of IL17induced VEGF secretion. PMID: 29039484
20. IL-17 contributes to lung obliterative bronchiolitis pathogenesis through regulating macrophages function PMID: 28863322
21. we demonstrate that gammadelta T cells and CD4+ T (Th17) cells are the two major producers of IL-17A in the lung at the early and later stages of chlamydial infection, respectively PMID: 27796286
22. In mice on a C57BL/6 background, neither IL-23p19 nor IL-17A plays a role for immune protection against L. major in the physiological context of natural infections. PMID: 27297018
23. IL-17A and IL-17F exert distinct biological effects during pulmonary infection; the IL-17F/IL-17RC signaling axis has the potential to significantly worsen pathogen-associated inflammation of the lower respiratory tract. PMID: 28813677
24. TLR2/4-mediated IL-17A inflammatory signaling is involved in vessel degeneration and revascularization, indicating that modulation of the TLR2/4-IL-17A pathway may be a novel therapeutic strategy for degenerative diseases. PMID: 27297042
25. The hormone levels are significantly reduced and lymphocytic infiltration in the lacrimal gland in ovariectomized mice, whereas the frequency of Th17 cells in the blood and spleen and IL-17A and IL-23 expression in the lacrimal glands are increased, leading to reduced tear production and positive fluorescein staining in the cornea. PMID: 27341090
26. the results suggest that IL-17A induces podocyte injury by activating the NLRP3 inflammasome and IL-1beta secretion and contributes to disruption of the kidney's filtration system. PMID: 29446486
27. These results suggest that a low concentration of IL-17A is likely to promote autophagic activity via activating RANKL-JNK pathway during osteoclastogenesis. PMID: 29476739
28. study shows that IL-17A plays an important role in comorbid depression associated with psoriatic inflammation, where both NFkappaB and p38MAPK pathways play significant roles via upregulation of inflammatory mediators in the brain PMID: 28570931
29. the present study demonstrated that IL-17A crucially regulated the wound healing process and that accelerated neutrophil accumulation caused by IL-17A led to the delayed wound repair. PMID: 27305096
30. The results emphasize the importance of IL-17 in experimental autoimmune myasthenia gravis development and that IL-17 independent pathways drive the autoimmune reaction. PMID: 28599246
31. In estrogen receptor negative breast cancer cells targeting of IL-17A inhibited PDL1 expression in the tumor microenvironment, decreasing the percentage of Treg cells in tumor-infiltrating lymphocytes, and promoting CD4+ and CD8+ T cells to secrete interferon gamma. PMID: 27935862
32. Report provides evidence that IL-17 can promote Lewis lung carcinoma growth through inhibition of myeloid-derived suppressor cells apoptosis, which maybe dependent on ERK1/2 signaling pathway. PMID: 28002798
33. these data provide novel insight into a dynamic IL-17A-CXCR2-neutrophil axis during acute segmented filamentous bacteria colonization and demonstrate a central role for neutrophils in limiting segmented filamentous bacteria expansion PMID: 27624780
34. Transient AIEC colonization in IL-17 KO mice resulted in increased intestinal epithelial damage, systemic bacterial burden and mortality compared with controls. IL-17 is required for the induction of IL-22 during AIEC strain E. coli LF82 colonization. IL-17 plays a protective role in AIEC strain E. coli LF82 induced colitis by promoting IL-22 secretion. PMID: 29195141
35. after orthotopic lung transplantation, in the IL-17A KO group, less inflammation in the bronchovascular axis was observed and a non-significant trend towards less bronchovascular fibrosis, pleural/septal inflammation and fibrosis, and parenchymal inflammation and fibrosis when compared to WT mice PMID: 27737799
36. Data show that IL-17 in the serum of collagen-induced arthritis (CIA) mice was markedly increased on day 14 and reached its apogee on day 27. PMID: 27356747
37. this study unveiled the role of IL-23-dependent IL-17 induction in LdCen-/- parasite-induced immunity and subsequent protection against visceral leishmaniasis PMID: 29187586
38. There was a significantly decreased percentage of IL-17A-producing CD4 T cells in mice receiving Tregs from xIAP mice. xIAP appears dispensable for the generation of induced Treg cells as well as function of natural Treg cells. There appeared to be a role of xIAP in generation of IL-17-producing cells from either naive CD4 T cells or Treg cells. PMID: 26825770
39. astrocytic IL-17A plays important roles in the maintenance of neuropathic pain through CaMKII/CREB signaling pathway in spinal cord. PMID: 26166359
40. Results reveal the importance of the IL-23/IL-17 inflammatory axis in secondary brain injury after intracerebral hemorrhage. PMID: 27729335
41. these results demonstrate an important role of CXCR6 in the regulation of pathological Th17 and IL-17A(+)TCRgammadelta(+) T-cell recruitment into atherosclerotic lesions. PMID: 26614640
42. These results suggest that IL-17A plays an important role in host survival against Toxoplasma gondii infection by protecting the host from an anaphylactic reaction via the downregulation of Toxoplasma gondii HSP70 and IFN-gamma production. PMID: 28893913
43. These results suggest that AKI after septic shock is driven through IL-17 release by Th17 cells; this is gradually consumed in the kidney. PMID: 27515003
44. IL-17A markedly induced VEGF and IL-6 expression in the Raw264.7 murine macrophage cell line and in the mouse corneal fibroblasts. PMID: 27419340
45. Vgamma4 T cells accelerate skin graft rejection by providing an early source of IL-17A PMID: 28733202
46. IL-17 inhibits adipogenesis where a lack of IL-17 ameliorates glucose metabolism. As well, the inhibition of TBK1 reduces inflammation induced by IL-17. Therefore, IL-17 may be involved in the development of obesity and metabolic dysfunction in a TBK1-dependent manner. PMID: 28237848
47. Th17 cells and TGFbeta1 are not required for the maintenance of gammadelta T cells producing interleukin-17A cells. PMID: 27649780
48. Data show that inducible T cell co-stimulator (ICOS) deficient mice have a significant increase in the population of IL-17-producing Vgamma2+ gammadelta T cells in the thymus, spleen, lymph nodes and skin and exhibit exacerbated sensitization responses to 2,4-dinitrofluorobenzene. PMID: 27235509
49. the majority of gammadelta T cells in the non-pregnant uterus, pregnant uterus, decidua and placenta of mice express the transcription factor RORgammat and produce interleukin-17 (IL-17). PMID: 27241697
50. In both the high-glucose - treated Muller cells and Akita mouse retina, the Act1/TRAF6/IKK/NF-kappaB signaling pathway was activated. IL-17A further enhanced inflammatory signaling activation, whereas Act1 knockdown or IKK inhibition blocked the downstream signaling activation by IL-17A. PMID: 27980343

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Secreted.

IL-17 family

Expressed by Th17 cell lineage (at protein level). The expression pattern reflects the differentiation state, with IL17A-IL17F heterodimers produced at higher levels than IL17A-IL17A and IL17F-IL17F dimers in fully differentiated Th17 cells. Expressed in

KEGG: mmu:16171

STRING: 10090.ENSMUSP00000027061

UniGene: Mm.5419