Interplay between IL-17 cytokines and gut microbiota in colon inflammation

Year 2025, Volume: 39 Issue: 4, 329 - 338, 30.10.2025

Ayşe Naz Özabacı

https://doi.org/10.18614/dehm.1813858

Abstract

This review aims to investigate the relationship between the gut microbiota and the interleukin-17 (IL-17) cytokine family, focusing on the effects of these interactions on immune homeostasis and disease pathogenesis. Based on recent findings, the role of IL-17 in maintaining gut integrity and regulating microbial composition has been examined. It explores how IL-17 influences the balance of gut microbiota and how microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), regulate IL-17 activity. The interaction between IL-17 and the gut microbiota has been addressed in the context of immune modulation across various mucosal sites. The results demonstrate that IL-17 plays a central role in maintaining mucosal defenses and shaping systemic immune responses. Disruption of this relationship may lead to autoimmune and inflammatory diseases, suggesting that targeting IL-17-microbiota interactions could offer new therapeutic approaches. This study seeks to shed light on the regulatory dynamics between IL-17 and the gut microbiota, extending beyond the functions of the immune system to inspire the development of novel therapeutic strategies for restoring homeostasis and alleviating inflammatory disorders.

Keywords

Colon inflammation , commensal microorganisms , gut microbiota , infection , IL-17 , IL-17A , IL-17F

References

• 1. A Brevi A, et al. Much more than IL-17A: Cytokines of the IL-17 family between microbiota and cancer. Front Immunol. 2020;11:565470. doi:10.3389/fimmu.2020.565470.
• 2. Nishio J, Honda K. Immunoregulation by the gut microbiota. Cell Mol Life Sci. 2012;69(21):3635-3650. doi:10.1007/s00018-012-0993-6.
• 3. Ivanov II, et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe. 2008;4(4):337-349. doi:10.1016/j.chom.2008.09.009.
• 4. Kamada N, Chen GY, Inohara N, Núñez G. Control of pathogens and pathobionts by the gut microbiota. Nat Immunol. 2013;14(7):685-690. doi:10.1038/ni.2608.
• 5. Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232. doi:10.1038/nri.2017.7.
• 6. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9(5):313-323. doi:10.1038/nri2515.
• 7. Tilg H, Kaser A. Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest. 2011;121(6):2126-2132. doi:10.1172/JCI58109.
• 8. Kamada N, Núñez G. Regulation of the immune system by the resident intestinal bacteria. Gastroenterology. 2014;146(6):1477-1488. doi:10.1053/j.gastro.2014.01.060.
• 9. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148(6):1258-1270. doi:10.1016/j.cell.2012.01.035.
• 10. Littman DR, Pamer EG. Role of the commensal microbiota in normal and pathogenic host immune responses. Cell Host Microbe. 2011;10(4):311-323. doi:10.1016/j.chom.2011.10.004.
• 11. Goepfert A, Lehmann S, Wirth E, Rondeau JM. The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties. Sci Rep. 2017;7(1):8906. doi:10.1038/s41598-017-08360-9.
• 12. Lücke J, Shiri AM, Zhang T, Kempski J, Giannou AD, Huber S. Rationalizing heptadecaphobia: Th17 cells and associated cytokines in cancer and metastasis. FEBS J. 2021;288(24):6942-6971. doi:10.1111/febs.15711.
• 13. Jiraskova Zakostelska Z, Reiss Z, Tlaskalova-Hogenova H, Rob F. Paradoxical reactions to anti-TNFα and anti-IL-17 treatment in psoriasis patients: Are skin and/or gut microbiota involved? Dermatol Ther (Heidelb). 2023;13(4):911-933. doi:10.1007/s13555-023-00904-4.
• 14. Yasuda K, Takeuchi Y, Hirota K. The pathogenicity of Th17 cells in autoimmune diseases. Semin Immunopathol. 2019;41(3):283-297. doi:10.1007/s00281-019-00733-8.
• 15. Friedrich M, Diegelmann J, Schauber J, Auernhammer CJ, Brand S. Intestinal neuroendocrine cells and goblet cells are mediators of IL-17A-amplified epithelial IL-17C production in human inflammatory bowel disease. Mucosal Immunol. 2015;8(4):943-958. doi:10.1038/mi.2014.124.
• 16. Song M, et al. IL-17A functions and the therapeutic use of IL-17A and IL-17RA targeted antibodies for cancer treatment. Int Immunopharmacol. 2023;123:110757. doi:10.1016/j.intimp.2023.110757.
• 17. Akhter S, et al. Role of Th17 and IL-17 cytokines on inflammatory and autoimmune diseases. Curr Pharm Des. 2023;29(26):2078-2090. doi:10.2174/1381612829666230904150808.
• 18. Wang F, et al. IL-17C has a pathogenic role in kidney ischemia/reperfusion injury. Kidney Int. 2020;97(6):1219-1229. doi:10.1016/j.kint.2020.01.015.
• 19. Iwakura Y, Nakae S, Saijo S, Ishigame H. The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol Rev. 2008;226(1):57-79. doi:10.1111/j.1600-065X.2008.00699.x.
• 20. Yamada H. Current perspectives on the role of IL-17 in autoimmune disease. J Inflamm Res. 2010;3:33-41. doi:10.2147/JIR.S6375.
• 21. Shabgah AG, Fattahi E, Shahneh FZ. Interleukin-17 in human inflammatory diseases. Adv Dermatol Allergol. 2014;4:256-261. doi:10.5114/pdia.2014.40954.
• 22. Ernst M, Putoczki T. IL-17 cuts to the chase in colon cancer. Immunity. 2014;41(6):880-882. doi:10.1016/j.immuni.2014.12.004.
• 23. Song X, Qian Y. The activation and regulation of IL-17 receptor mediated signaling. Cytokine. 2013;62(2):175-182. doi:10.1016/j.cyto.2013.03.014.
• 24. Monin L, Gaffen SL. Interleukin-17 family cytokines: signaling mechanisms, biological activities, and therapeutic implications. Cold Spring Harb Perspect Biol. 2018;10(4):a028522. doi:10.1101/cshperspect.a028522.
• 25. Koh CH, Kim BS, Kang CY, Chung Y, Seo H. IL-17 and IL-21: their immunobiology and therapeutic potentials. Immune Netw. 2024;24(1):e2. doi:10.4110/in.2024.24.e2.
• 26. Islam MR, Aziz MA, Shahriar M, Islam MS. Polymorphisms in IL-17A gene and susceptibility of colorectal cancer in Bangladeshi population: a case-control analysis. Cancer Control. 2022;29:107327482211438. doi:10.1177/10732748221143879.
• 27. Ge Y, Huang M, Yao Y. Biology of interleukin-17 and its pathophysiological significance in sepsis. Front Immunol. 2020;11:1558. doi:10.3389/fimmu.2020.01558.
• 28. Feng WQ, et al. IL-17A-mediated mitochondrial dysfunction induces pyroptosis in colorectal cancer cells and promotes CD8+ T-cell tumour infiltration. J Transl Med. 2023;21(1):335. doi:10.1186/s12967-023-04187-3.
• 29. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823-1836. doi:10.1042/BCJ20160510.
• 30. Okamura Y, Kinoshita M, Kono T, Sakai M, Hikima J. Deficiency of interleukin-17 receptor A1 induces microbiota disruption in the intestine of Japanese medaka, Oryzias latipes. Comp Biochem Physiol D. 2021;40:100885. doi:10.1016/j.cbd.2021.100885.
• 31. Douzandeh-Mobarrez B, Kariminik A. Gut microbiota and IL-17A: physiological and pathological responses. Probiotics Antimicrob Proteins. 2019;11(1):1-10. doi:10.1007/s12602-017-9329-z.
• 32. Wu HJ, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes. 2012;3(1):4-14. doi:10.4161/gmic.19320.
• 33. Portincasa P, et al. Gut microbiota and short chain fatty acids: implications in glucose homeostasis. Int J Mol Sci. 2022;23(3):1105. doi:10.3390/ijms23031105.
• 34. Vallianou NG, et al. Gut microbiota and its role in the brain-gut-kidney axis in hypertension. Curr Hypertens Rep. 2023;25(11):367-376. doi:10.1007/s11906-023-01263-3.
• 35. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54(9):2325-2340. doi:10.1194/jlr.R036012.
• 36. Cheng H, Guan X, Chen D, Ma W. The Th17/Treg cell balance: a gut microbiota-modulated story. Microorganisms. 2019;7(12):583. doi:10.3390/microorganisms7120583.
• 37. Calcinotto A, et al. Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. Nat Commun. 2018;9(1):4832. doi:10.1038/s41467-018-07305-8.
• 38. Dupraz L, et al. Gut microbiota-derived short-chain fatty acids regulate IL-17 production by mouse and human intestinal γδ T cells. Cell Rep. 2021;36(1):109332. doi:10.1016/j.celrep.2021.109332.
• 39. Zhu FL, et al. Taurine regulates the expression of interleukin-17/10 and intestinal flora and protects the liver and intestinal mucosa in a nonalcoholic fatty liver disease rat model. Diabetes Metab Syndr Obes. 2024;17:675-689. doi:10.2147/DMSO.S440978.
• 40. Chen YJ, et al. Short-chain fatty acids ameliorate imiquimod-induced skin thickening and IL-17 levels and alter gut microbiota in mice: a metagenomic association analysis. Sci Rep. 2024;14(1):17495. doi:10.1038/s41598-024-67325-x.
• 41. Biton M, et al. T helper cell cytokines modulate intestinal stem cell renewal and differentiation. Cell. 2018;175(5):1307-1320.e22. doi:10.1016/j.cell.2018.10.008.
• 42. Regen T, et al. IL-17 controls central nervous system autoimmunity through the intestinal microbiome. Sci Immunol. 2021;6(56):eaz6563. doi:10.1126/sciimmunol.aaz6563.
• 43. Bellone M, Brevi A, Huber S. Microbiota-propelled T helper 17 cells in inflammatory diseases and cancer. Microbiol Mol Biol Rev. 2020;84(2):e00064-19. doi:10.1128/MMBR.00064-19.
• 44. Singh AK, et al. RORγt-Raftlin1 complex regulates the pathogenicity of Th17 cells and colonic inflammation. Nat Commun. 2023;14(1):4972. doi:10.1038/s41467-023-40622-1.
• 45. Atarashi K, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331(6015):337-341. doi:10.1126/science.1198469.
• 46. Alexander M, et al. Human gut bacterial metabolism drives Th17 activation and colitis. Cell Host Microbe. 2022;30(1):17-30.e9. doi:10.1016/j.chom.2021.11.001.
• 47. Beringer A, Noack M, Miossec P. IL-17 in chronic inflammation: from discovery to targeting. Trends Mol Med. 2016;22(3):230-241. doi:10.1016/j.molmed.2016.01.001.
• 48. Noviello D, Mager R, Roda G, Borroni RG, Fiorino G, Vetrano S. The IL23-IL17 immune axis in the treatment of ulcerative colitis: successes, defeats, and ongoing challenges. Front Immunol. 2021;12:611256. doi:10.3389/fimmu.2021.611256.
• 49. Deng Z, Wang S, Wu C, Wang C. IL-17 inhibitor-associated inflammatory bowel disease: a study based on literature and database analysis. Front Pharmacol. 2023;14:1124628. doi:10.3389/fphar.2023.1124628.
• 50. Țiburcă L, et al. The treatment with interleukin-17 inhibitors and immune-mediated inflammatory diseases. Curr Issues Mol Biol. 2022;44(5):1851-1866. doi:10.3390/cimb44050127.
• 51. Li Y, et al. Gut microbiota disorder contributes to the production of IL-17A that exerts chemotaxis via binding to IL-17RA in endometriosis. J Inflamm Res. 2024;17:4199-4217. doi:10.2147/JIR.S458928.