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Review Article

Th17 cells: A new target in kidney disease research

ORCID Icon, , , , , & ORCID Icon show all
Received 28 Aug 2023, Accepted 09 Jan 2024, Published online: 05 Mar 2024

References

  • Bello AK, Levin A, Tonelli M, et al. Assessment of global kidney health care status. JAMA 2017;317(18):1864–1881. doi:10.1001/jama.2017.4046.
  • Levin A, Tonelli M, Bonventre J, et al. Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy. Lancet 2017;390(10105):1888–1917. doi:10.1016/s0140-6736(17)30788-2.
  • Jager KJ, Kovesdy C, Langham R, et al. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Kidney Int 2019;96(5):1048–1050. doi:10.1016/j.kint.2019.07.012.
  • Xu J, Li X, Yuan Q, et al. The semaphorin 4A-neuropilin 1 axis alleviates kidney ischemia reperfusion injury by promoting the stability and function of regulatory T cells. Kidney Int 2021;100(6):1268–1281. doi:10.1016/j.kint.2021.08.023.
  • Rose A, VON Spee-Mayer C, Kloke L, et al. IL-2 therapy diminishes renal inflammation and the activity of kidney-infiltrating CD4+ T cells in murine lupus nephritis. Cells 2019;8(10):1234. doi:10.3390/cells8101234.
  • Lee SA, Noel S, Kurzhagen JT, et al. CD4(+) T cell-derived NGAL modifies the outcome of ischemic acute kidney injury. J Immunol 2020;204(3):586–595. doi:10.4049/jimmunol.1900677.
  • Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 2005;6(11):1123–1132. doi:10.1038/ni1254.
  • Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005;6(11):1133–1141. doi:10.1038/ni1261.
  • Wynn TA. T(H)-17: a giant step from T(H)1 and T(H)2. Nat Immunol 2005;6(11):1069–1070. doi:10.1038/ni1105-1069.
  • Mcallister F, Henry A, Kreindler JL, et al. Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth- related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J Immunol 2005;175(1):404–412. doi:10.4049/jimmunol.175.1.404.
  • Toy D, Kugler D, Wolfson M, et al. Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol 2006;177(1):36–39. doi:10.4049/jimmunol.177.1.36.
  • Yang XO, Pappu BP, Nurieva R, et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 2008;28(1):29–39. doi:10.1016/j.immuni.2007.11.016.
  • Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol 2010;40(7):1830–1835. doi:10.1002/eji.201040391.
  • Stepkowski SM, Chen W, Ross JA, et al. STAT3: an important regulator of multiple cytokine functions. Transplantation. 2008;85(10):1372–1377. doi:10.1097/TP.0b013e3181739d25.
  • Korn T, Bettelli E, Gao W, et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature. 2007;448(7152):484–487. doi:10.1038/nature05970.
  • Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005;201(2):233–240. doi:10.1084/jem.20041257.
  • Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006;441(7090):235–238. doi:10.1038/nature04753.
  • Harbour SN, Ditoro DF, Witte SJ, et al. TH17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity. Sci Immunol 2020;5(49):eaaw2262. doi:10.1126/sciimmunol.aaw2262.
  • Biswas PS. IL-17 in renal immunity and autoimmunity. J Immunol 2018;201(11):3153–3159. doi:10.4049/jimmunol.1801042.
  • Nastase MV, Zeng-Brouwers J, Beckmann J, et al. Biglycan, a novel trigger of Th1 and Th17 cell recruitment into the kidney. Matrix Biol 2018;68–69:293–317. doi:10.1016/j.matbio.2017.12.002.
  • Lu G, Zhang X, Shen L, et al. CCL20 secreted from IgA1-stimulated human mesangial cells recruits inflammatory Th17 cells in IgA nephropathy. PLOS One 2017;12(5):e0178352. doi:10.1371/journal.pone.0178352.
  • Meitei HT, Jadhav N, Lal G. CCR6-CCL20 axis as a therapeutic target for autoimmune diseases. Autoimmun Rev 2021;20(7):102846. doi:10.1016/j.autrev.2021.102846.
  • Paust HJ, Turner JE, Riedel JH, et al. Chemokines play a critical role in the cross-regulation of Th1 and Th17 immune responses in murine crescentic glomerulonephritis. Kidney Int 2012;82(1):72–83. doi:10.1038/ki.2012.101.
  • Schmidt T, Luebbe J, Kilian C, et al. IL-17 receptor C signaling controls CD4(+) TH17 immune responses and tissue injury in immune-mediated kidney diseases. J Am Soc Nephrol 2021;32(12):3081–3098. doi:10.1681/asn.2021030426.
  • Loverre A, Tataranni T, Castellano G, et al. IL-17 expression by tubular epithelial cells in renal transplant recipients with acute antibody-mediated rejection. Am J Transplant 2011;11(6):1248–1259. doi:10.1111/j.1600-6143.2011.03529.x.
  • Krohn S, Nies JF, Kapffer S, et al. IL-17C/IL-17 receptor E signaling in CD4(+) T cells promotes TH17 cell-driven glomerular inflammation. J Am Soc Nephrol 2018;29(4):1210–1222. doi:10.1681/asn.2017090949.
  • Ramani K, Jawale CV, Verma AH, et al. Unexpected kidney-restricted role for IL-17 receptor signaling in defense against systemic Candida albicans infection. JCI Insight 2018;3(9):e98241. doi:10.1172/jci.insight.98241.
  • Liu Y, Su L, Lin Q, et al. Induction of C-Mip by IL-17 plays an important role in adriamycin-induced podocyte damage. Cell Physiol Biochem 2015;36(4):1274–1290. doi:10.1159/000430296.
  • Mills KHG. IL-17 and IL-17-producing cells in protection versus pathology. Nat Rev Immunol 2023;23(1):38–54. doi:10.1038/s41577-022-00746-9.
  • Conti HR, Shen F, Nayyar N, et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med 2009;206(2):299–311. doi:10.1084/jem.20081463.
  • Bai H, Gao X, Zhao L, et al. Respective IL-17A production by gammadelta T and Th17 cells and its implication in host defense against chlamydial lung infection. Cell Mol Immunol 2017;14(10):850–861. doi:10.1038/cmi.2016.53.
  • St Leger AJ, Hansen AM, Karauzum H, et al. STAT-3-independent production of IL-17 by mouse innate-like alpha beta T cells controls ocular infection. J Exp Med 2018;215(4):1079–1090. doi:10.1084/jem.20170369.
  • Ueno A, Jeffery L, Kobayashi T, et al. Th17 plasticity and its relevance to inflammatory bowel disease. J Autoimmun 2018;87:38–49. doi:10.1016/j.jaut.2017.12.004.
  • Ivanov II, Mckenzie BS, Zhou L, et al. The orphan nuclear receptor ROR gammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006;126(6):1121–1133. doi:10.1016/j.cell.2006.07.035.
  • Steinmetz OM, Summers SA, Gan PY, et al. The Th17-defining transcription factor RORgammat promotes glomerulonephritis. J Am Soc Nephrol 2011;22(3):472–483. doi:10.1681/asn.2010040435.
  • Lee H, Lee JW, Yoo KD, et al. Cln 3-requiring 9 is a negative regulator of Th17 pathway-driven inflammation in anti-glomerular basement membrane glomerulonephritis. Am J Physiol Renal Physiol 2016;311(3):F505–19. doi:10.1152/ajprenal.00533.2015.
  • Paust HJ, Turner JE, Steinmetz OM, et al. The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis. J Am Soc Nephrol 2009;20(5):969–979. doi:10.1681/asn.2008050556.
  • Disteldorf EM, Krebs CF, Paust HJ, et al. CXCL5 drives neutrophil recruitment in TH17-mediated GN. J Am Soc Nephrol 2015;26(1):55–66. doi:10.1681/asn.2013101061.
  • Kluger MA, Meyer MC, Nosko A, et al. RORgammat(+)Foxp3(+) cells are an independent bifunctional regulatory T cell lineage and mediate crescentic GN. J Am Soc Nephrol 2016;27(2):454–465. doi:10.1681/asn.2014090880.
  • Turner JE, Krebs C, Tittel AP, et al. IL-17A production by renal gammadelta T cells promotes kidney injury in crescentic GN. J Am Soc Nephrol 2012;23(9):1486–1495. doi:10.1681/asn.2012010040.
  • Velden J, Paust HJ, Hoxha E, et al. Renal IL-17 expression in human ANCA-associated glomerulonephritis. Am J Physiol Renal Physiol 2012;302(12):F1663–73. doi:10.1152/ajprenal.00683.2011.
  • Diefenhardt P, Nosko A, Kluger MA, et al. IL-10 receptor signaling empowers regulatory T cells to control Th17 responses and protect from GN. J Am Soc Nephrol 2018;29(7):1825–1837. doi:10.1681/asn.2017091044.
  • Schreiber A, Rousselle A, Klocke J, et al. Neutrophil gelatinase-associated lipocalin protects from ANCA-induced GN by inhibiting TH17 immunity. J Am Soc Nephrol 2020;31(7):1569–1584. doi:10.1681/asn.2019090879.
  • Kshirsagar S, Riedl M, Billing H, et al. Akt-dependent enhanced migratory capacity of Th17 cells from children with lupus nephritis. J Immunol 2014;193(10):4895–4903. doi:10.4049/jimmunol.1400044.
  • Maeda K, Kosugi T, Sato W, et al. CD147/basigin limits lupus nephritis and Th17 cell differentiation in mice by inhibiting the interleukin-6/STAT-3 pathway. Arthritis Rheumatol 2015;67(8):2185–2195. doi:10.1002/art.39155.
  • Zhou X, Chen H, Wei F, et al. Alpha-mangostin attenuates pristane-induced lupus nephritis by regulating Th17 differentiation. Int J Rheum Dis 2020;23(1):74–83. doi:10.1111/1756-185x.13743.
  • Dai H, He F, Tsokos GC, et al. IL-23 limits the production of IL-2 and promotes autoimmunity in lupus. J Immunol 2017;199(3):903–910. doi:10.4049/jimmunol.1700418.
  • An JN, Ryu S, Kim YC, et al. NK1.1(-) natural killer T cells upregulate interleukin-17 expression in experimental lupus nephritis. Am J Physiol Renal Physiol 2021;320(5):F772–F788. doi:10.1152/ajprenal.00252.2020.
  • Du B, Fan X, Lei F, et al. Comparative transcriptome analysis reveals a potential role for CaMK4 in gammadeltaT17 cells from systemic lupus erythematosus patients with lupus nephritis. Int Immunopharmacol 2020;80:106139. doi:10.1016/j.intimp.2019.106139.
  • Meng T, Li X, Ao X, et al. Hemolytic Streptococcus may exacerbate kidney damage in IgA nephropathy through CCL20 response to the effect of Th17 cells. PLOS One 2014;9(9):e108723. doi:10.1371/journal.pone.0108723.
  • Wang J, Liu H, Yue G, et al. Human placenta-derived mesenchymal stem cells ameliorate diabetic kidney disease by modulating the T helper 17 cell/regulatory T-cell balance through the programmed death 1/programmed death-ligand 1 pathway. Diabetes Obes Metab 2024;26(1):32–45. doi:10.1111/dom.15282.
  • Wang D, Zhang Z, Si Z, et al. Dapagliflozin reverses the imbalance of T helper 17 and T regulatory cells by inhibiting SGK1 in a mouse model of diabetic kidney disease. FEBS Open Bio 2021;11(5):1395–1405. doi:10.1002/2211-5463.13147.
  • Zhang P, Song XY, Li W, et al. Study on the mechanism of Bu-Shen-He-Mai granules in improving renal damage of ageing spontaneously hypertensive rats by regulating Th17 Cell/Tregs balance. Evid Based Complement Alternat Med 2022;2022:8315503. doi:10.1155/2022/8315503.
  • Luo C, Luo F, Man X, et al. Mesenchymal stem cells attenuate sepsis-associated acute kidney injury by changing the balance of Th17 cells/Tregs via Gal-9/Tim-3. Curr Stem Cell Res Ther 2023;18(4):540–550. doi:10.2174/1574888x17666220511151343.
  • Luo C, Luo F, Che L, et al. Mesenchymal stem cells protect against sepsis-associated acute kidney injury by inducing Gal-9/Tim-3 to remodel immune homeostasis. Ren Fail 2023;45(1):2187229. doi:10.1080/0886022x.2023.2187229.
  • Mehrotra P, Ullah MM, Collett JA, et al. Mutation of RORgammaT reveals a role for Th17 cells in both injury and recovery from renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 2020;319(5):F796–f808. doi:10.1152/ajprenal.00187.2020.
  • Mehrotra P, Sturek M, Neyra JA, et al. Calcium channel Orai1 promotes lymphocyte IL-17 expression and progressive kidney injury. J Clin Invest. 2019;129(11):4951–4961. doi:10.1172/jci126108.
  • Li L, Huang L, Vergis AL, et al. IL-17 produced by neutrophils regulates IFN-gamma-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury. J Clin Invest 2010;120(1):331–342. doi:10.1172/jci38702.
  • Mehrotra P, Collett JA, Mckinney SD, et al. IL-17 mediates neutrophil infiltration and renal fibrosis following recovery from ischemia reperfusion: compensatory role of natural killer cells in athymic rats. Am J Physiol Renal Physiol 211835902017;312(3):F385–F397. doi:10.1152/ajprenal.00462.2016.
  • Zhang J, Li Q, Zou YR, et al. HMGB1-TLR4-IL-23-IL-17A axis accelerates renal ischemia-reperfusion injury via the recruitment and migration of neutrophils. Int Immunopharmacol 2021;94:107433. doi:10.1016/j.intimp.2021.107433.
  • 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.
  • Mcgeachy MJ, Cua DJ, Gaffen SL. The IL-17 family of cytokines in health and disease. Immunity 2019;50(4):892–906. doi:10.1016/j.immuni.2019.03.021.
  • Lee SY, Lee SH, Seo HB, et al. Inhibition of IL-17 ameliorates systemic lupus erythematosus in Roquin(san/san) mice through regulating the balance of TFH cells, GC B cells, Treg and Breg. Sci Rep 2019;9(1):5227. doi:10.1038/s41598-019-41534-1.
  • Ma J, Li YJ, Chen X, et al. Interleukin 17A promotes diabetic kidney injury. Sci Rep 2019;9(1):2264. doi:10.1038/s41598-019-38811-4.
  • Collett JA, Ortiz-Soriano V, Li X, et al. Serum IL-17 levels are higher in critically ill patients with AKI and associated with worse outcomes. Crit Care 2022;26(1):107. doi:10.1186/s13054-022-03976-4.
  • Krebs CF, Reimers D, Zhao Y, et al. Pathogen-induced tissue-resident memory TH17 (TRM17) cells amplify autoimmune kidney disease. Sci Immunol 2020;5(50):eaba4163. doi:10.1126/sciimmunol.aba4163.
  • Chadban SJ, Atkins RC. Glomerulonephritis. Lancet 2005;365(9473):1797–1806. doi:10.1016/s0140-6736(05)66583-x.
  • Krebs CF, Kapffer S, Paust HJ, et al. MicroRNA-155 drives TH17 immune response and tissue injury in experimental crescentic GN. J Am Soc Nephrol 2013;24(12):1955–1965. doi:10.1681/asn.2013020130.
  • Kluger MA, Luig M, Wegscheid C, et al. Stat3 programs Th17-specific regulatory T cells to control GN. J Am Soc Nephrol. 2014;25(6):1291–1302. doi:10.1681/asn.2013080904.
  • Gan PY, Steinmetz OM, Tan DS, et al. Th17 cells promote autoimmune anti-myeloperoxidase glomerulonephritis. J Am Soc Nephrol 2010;21(6):925–931. doi:10.1681/asn.2009070763.
  • Watanabe S, Zhang Y, Fukusumi Y, et al. Th17 cells participate in Thy1.1 glomerulonephritis which is ameliorated by tacrolimus. Am J Nephrol 2022;53(5):388–396. doi:10.1159/000524111.
  • Summers SA, Steinmetz OM, Li M, et al. Th1 and Th17 cells induce proliferative glomerulonephritis. J Am Soc Nephrol 2009;20(12):2518–2524. doi:10.1681/asn.2009030337.
  • Krebs CF, Panzer U. Plasticity and heterogeneity of Th17 in immune-mediated kidney diseases. J Autoimmun 2018;87:61–68. doi:10.1016/j.jaut.2017.12.005.
  • Krebs CF, Schmidt T, Riedel JH, et al. T helper type 17 cells in immune-mediated glomerular disease. Nat Rev Nephrol 2017;13(10):647–659. doi:10.1038/nrneph.2017.112.
  • Gan PY, Chan A, Ooi JD, et al. Biologicals targeting T helper cell subset differentiating cytokines are effective in the treatment of murine anti-myeloperoxidase glomerulonephritis. Kidney Int 2019;96(5):1121–1133. doi:10.1016/j.kint.2019.05.012.
  • Hamour S, Gan PY, Pepper R, et al. Local IL-17 production exerts a protective role in murine experimental glomerulonephritis. PLOS One 2015;10(8):e0136238. doi:10.1371/journal.pone.0136238.
  • Paquissi FC, Abensur H. The Th17/IL-17 axis and kidney diseases, with focus on lupus nephritis. Front Med 2021;8:654912. doi:10.3389/fmed.2021.654912.
  • Larosa M, Zen M, Gatto M, et al. IL-12 and IL-23/Th17 axis in systemic lupus erythematosus. Exp Biol Med. 2019;244(1):42–51. doi:10.1177/1535370218824547.
  • Dedong H, Feiyan Z, Jie S, et al. Analysis of interleukin-17 and interleukin-23 for estimating disease activity and predicting the response to treatment in active lupus nephritis patients. Immunol Lett 2019;210:33–39. doi:10.1016/j.imlet.2019.04.002.
  • Cheng Y, Yang X, Zhang X, et al. Analysis of expression levels of IL-17 and IL-34 and influencing factors for prognosis in patients with lupus nephritis. Exp Ther Med 2019;17(3):2279–2283. doi:10.3892/etm.2019.7168.
  • Zhang Z, Kyttaris VC, Tsokos GC. The role of IL-23/IL-17 axis in lupus nephritis. J Immunol 2009;183(5):3160–3169. doi:10.4049/jimmunol.0900385.
  • Kyttaris VC, Zhang Z, Kuchroo VK, et al. Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice. J Immunol 2010;184(9):4605–4609. doi:10.4049/jimmunol.0903595.
  • Schmidt T, Paust HJ, Krebs CF, et al. Function of the Th17/interleukin-17A immune response in murine lupus nephritis. Arthritis Rheumatol 2015;67(2):475–487. doi:10.1002/art.38955.
  • Jakiela B, Kosałka J, Plutecka H, et al. Facilitated expansion of Th17 cells in lupus nephritis patients. Clin Exp Immunol. 2018;194(3):283–294. doi:10.1111/cei.13196.
  • Le W, Liang S, Hu Y, et al. Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol Dial Transplant 2012;27(4):1479–1485. doi:10.1093/ndt/gfr527.
  • Koyama A, Igarashi M, Kobayashi M. Natural history and risk factors for immunoglobulin A nephropathy in Japan. Research group on progressive renal diseases. Am J Kidney Dis 1997;29(4):526–532. doi:10.1016/s0272-6386(97)90333-4.
  • Liao H, Huang Z, Zhang J, et al. Association of genetic polymorphisms in IL-23R and IL-17A with the susceptibility to IgA nephropathy in a Chinese Han population. Genes Immun 2022;23(1):33–41. doi:10.1038/s41435-021-00160-6.
  • Mitsdoerffer M, Lee Y, Jäger A, et al. Proinflammatory T helper type 17 cells are effective B-cell helpers. Proc Natl Acad Sci USA 2010;107(32):14292–14297. doi:10.1073/pnas.1009234107.
  • Luo R, Cheng Y, Chang D, et al. Tertiary lymphoid organs are associated with the progression of kidney damage and regulated by interleukin-17A. Theranostics 2021;11(1):117–131. doi:10.7150/thno.48624.
  • Ku E, Lee BJ, Wei J, et al. Hypertension in CKD: core curriculum 2019. Am J Kidney Dis 2019;74(1):120–131. doi:10.1053/j.ajkd.2018.12.044.
  • Sievers LK, Eckardt KU. Molecular mechanisms of kidney injury and repair in arterial hypertension. Int J Mol Sci 2019;20(9):2138. doi:10.3390/ijms20092138.
  • Basile DP, Abais-Battad JM, Mattson DL. Contribution of Th17 cells to tissue injury in hypertension. Curr Opin Nephrol Hypertens 2021;30(2):151–158. doi:10.1097/mnh.0000000000000680.
  • Avery EG, Bartolomaeus H, Rauch A, et al. Quantifying the impact of gut microbiota on inflammation and hypertensive organ damage. Cardiovasc Res 2023;119(6):1441–1452. doi:10.1093/cvr/cvac121.
  • Du YN, Tang XF, Xu L, et al. SGK1-FoxO1 signaling pathway mediates Th17/Treg imbalance and target organ inflammation in angiotensin II-induced hypertension. Front Physiol 2018;9:1581. doi:10.3389/fphys.2018.01581.
  • de la Visitación N, Robles-Vera I, Toral M, et al. Gut microbiota contributes to the development of hypertension in a genetic mouse model of systemic lupus erythematosus. Br J Pharmacol 2021;178(18):3708–3729. doi:10.1111/bph.15512.
  • Krebs CF, Lange S, Niemann G, et al. Deficiency of the interleukin 17/23 axis accelerates renal injury in mice with deoxycorticosterone acetate + angiotensin II-induced hypertension. Hypertension 2014;63(3):565–571. doi:10.1161/hypertensionaha.113.02620.
  • Niewczas MA, Pavkov ME, Skupien J, et al. A signature of circulating inflammatory proteins and development of end- stage renal disease in diabetes. Nat Med 2019;25(5):805–813. doi:10.1038/s41591-019-0415-5.
  • May CJ, Welsh GI, Chesor M, et al. Human Th17 cells produce a soluble mediator that increases podocyte motility via signaling pathways that mimic PAR-1 activation. Am J Physiol Renal Physiol 2019;317(4):F913–F921. doi:10.1152/ajprenal.00093.2019.
  • Zhai S, Sun B, Zhang Y, et al. IL-17 aggravates renal injury by promoting podocyte injury in children with primary nephrotic syndrome. Exp Ther Med 2020;20(1):409–417. doi:10.3892/etm.2020.8698.
  • Lavoz C, Matus YS, Orejudo M, et al. Interleukin-17A blockade reduces albuminuria and kidney injury in an accelerated model of diabetic nephropathy. Kidney Int 2019;95(6):1418–1432. doi:10.1016/j.kint.2018.12.031.
  • Mohamed R, Jayakumar C, Chen F, et al. Low-dose IL-17 therapy prevents and reverses diabetic nephropathy, metabolic syndrome, and associated organ fibrosis. J Am Soc Nephrol 2016;27(3):745–765. doi:10.1681/asn.2014111136.
  • Pindjakova J, Hanley SA, Duffy MM, et al. Interleukin-1 accounts for intrarenal Th17 cell activation during ureteral obstruction. Kidney Int 2012;81(4):379–390. doi:10.1038/ki.2011.348.
  • Mehrotra P, Patel JB, Ivancic CM, et al. Th-17 cell activation in response to high salt following acute kidney injury is associated with progressive fibrosis and attenuated by AT-1R antagonism. Kidney Int 2015;88(4):776–784. doi:10.1038/ki.2015.200.
  • Yang XY, Song J, Hou SK, et al. Ulinastatin ameliorates acute kidney injury induced by crush syndrome inflammation by modulating Th17/Treg cells. Int Immunopharmacol 2020;81:106265. doi:10.1016/j.intimp.2020.106265.
  • Mehrotra P, Collett JA, Gunst SJ, et al. Th17 cells contribute to pulmonary fibrosis and inflammation during chronic kidney disease progression after acute ischemia. Am J Physiol Regul Integr Comp Physiol 2018;314(2):R265–R273. doi:10.1152/ajpregu.00147.2017.
  • Noel S. Orai1: CRACing the Th17 response in AKI. J Clin Invest 2019;129(11):4583–4586. doi:10.1172/jci131935.
  • Feng L, Li ZY, Wang L, et al. Wedelolactone-loaded micelles ameliorate doxorubicin-induced oxidative injury in podocytes by improving permeability and bioavailability. Front Bioeng Biotechnol 2019;7:333. doi:10.3389/fbioe.2019.00333.
  • Yan J, Li Y, Yang H, et al. Interleukin-17A participates in podocyte injury by inducing IL-1beta secretion through ROS-NLRP3 inflammasome-caspase-1 pathway. Scand J Immunol 2018;87(4):e12645. doi:10.1111/sji.12645.
  • Noubade R, Krementsov DN, DEL Rio R, et al. Activation of p38 MAPK in CD4 T cells controls IL-17 production and autoimmune encephalomyelitis. Blood 2011;118(12):3290–3300. doi:10.1182/blood-2011-02-336552.
  • Amit A, Dikhit MR, Singh, AK, et al. Immunization with Leishmania donovani protein disulfide isomerase DNA construct induces Th1 and Th17 dependent immune response and protection against experimental visceral leishmaniasis in Balb/c mice. Mol Immunol 2017;82:104–113. doi:10.1016/j.molimm.2016.12.022.
  • Zhao Z, Wang Y, Gao Y, et al. The PRAK-NRF2 axis promotes the differentiation of Th17 cells by mediating the redox homeostasis and glycolysis. Proc Natl Acad Sci USA 2023;120(19):e2212613120. doi:10.1073/pnas.2212613120.
  • Zhao M, Chen H, Ding Q, et al. Nuclear factor erythroid 2-related factor 2 deficiency exacerbates lupus nephritis in B6/lpr mice by regulating Th17 cell function. Sci Rep 2016;6(1):38619. doi:10.1038/srep38619.
  • Hernández G, Lal H, Fidalgo M, et al. A novel cardioprotective p38-MAPK/mTOR pathway. Exp Cell Res 2011;317(20):2938–2949. doi:10.1016/j.yexcr.2011.09.011.
  • Kma L, Baruah TJ. The interplay of ROS and the PI3K/Akt pathway in autophagy regulation. Biotechnol Appl Biochem 2022;69(1):248–264. doi:10.1002/bab.2104.
  • Cluxton D, Petrasca A, Moran B, et al. Differential regulation of human Treg and Th17 cells by fatty acid synthesis and glycolysis. Front Immunol 2019;10:115. doi:10.3389/fimmu.2019.00115.
  • Shi L Z, Wang R, Huang G, et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 2011;208(7):1367–1376. doi:10.1084/jem.20110278.
  • Wagner A, Wang C, Fessler J, et al. Metabolic modeling of single Th17 cells reveals regulators of autoimmunity. Cell 2021;184(16):4168–4185.e21. doi:10.1016/j.cell.2021.05.045.
  • Gerriets VA, Kishton RJ, Nichols AG, et al. Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. J Clin Invest 2015;125(1):194–207. doi:10.1172/jci76012.
  • Zhang Q, Wang L, Jiang J, et al. Critical role of AdipoR1 in regulating Th17 cell differentiation through modulation of HIF-1alpha-dependent glycolysis. Front Immunol 2020;11:2040. doi:10.3389/fimmu.2020.02040.
  • Berod L, Friedrich C, Nandan A, et al. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med 2014;20(11):1327–1333. doi:10.1038/nm.3704.
  • Endo Y, Asou HK, Matsugae N, et al. Obesity drives Th17 cell differentiation by inducing the lipid metabolic kinase, ACC1. Cell Rep 2015;12(6):1042–1055. doi:10.1016/j.celrep.2015.07.014.
  • Machacek M, Saunders H, Zhang Z, et al. Elevated O-GlcNAcylation enhances pro-inflammatory Th17 function by altering the intracellular lipid microenvironment. J Biol Chem 2019;294(22):8973–8990. doi:10.1074/jbc.RA119.008373.
  • Young KE, Flaherty S, Woodman KM, et al. Fatty acid synthase regulates the pathogenicity of Th17 cells. J Leukoc Biol 2017;102(5):1229–1235. doi:10.1189/jlb.3AB0417-159RR.
  • Berod L, Friedrich C, Nandan A, et al. Erratum: de novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med 2015;21(4):414–414. doi:10.1038/nm0415-414d.
  • Yuan J, Cai T, Zheng X, et al. Potentiating CD8(+) T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling. Protein Cell 2021;12(4):240–260. doi:10.1007/s13238-021-00821-2.
  • Hu X, Wang Y, Hao LY, et al. Sterol metabolism controls T(H)17 differentiation by generating endogenous RORgamma agonists. Nat Chem Biol 2015;11(2):141–147. doi:10.1038/nchembio.1714.
  • Eller P, Eller K, Wolf AM, et al. Atorvastatin attenuates murine anti-glomerular basement membrane glomerulonephritis. Kidney Int 2010;77(5):428–435. doi:10.1038/ki.2009.478.
  • Bentwich I, Avniel A, Karov Y, et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 2005;37(7):766–770. doi:10.1038/ng1590.
  • Berezikov E, Guryev V, VAN DE Belt J, et al. Phylogenetic shadowing and computational identification of human microRNA genes. Cell 2005;120(1):21–24. doi:10.1016/j.cell.2004.12.031.
  • Valihrach L, Androvic P, Kubista M. Circulating miRNA analysis for cancer diagnostics and therapy. Mol Aspects Med 2020;72:100825. doi:10.1016/j.mam.2019.10.002.
  • Mahtal N, Lenoir O, Tinel C, et al. MicroRNAs in kidney injury and disease. Nat Rev Nephrol 2022;18(10):643–662. doi:10.1038/s41581-022-00608-6.
  • Metzinger-Le Meuth V, Fourdinier O, Charnaux N, et al. The expanding roles of microRNAs in kidney pathophysiology. Nephrol Dial Transplant 2019;34(1):7–15. doi:10.1093/ndt/gfy140.
  • Xin Q, Li J, Dang J, et al. miR-155 deficiency ameliorates autoimmune inflammation of systemic lupus erythematosus by targeting S1pr1 in Faslpr/lpr mice. J Immunol 2015;194(11):5437–5445. doi:10.4049/jimmunol.1403028.
  • Lin X, You Y, Wang J, et al. MicroRNA-155 deficiency promotes nephrin acetylation and attenuates renal damage in hyperglycemia-induced nephropathy. Inflammation 2015;38(2):546–554. doi:10.1007/s10753-014-9961-7.
  • Leiss H, Salzberger W, Jacobs B, et al. MicroRNA 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus. PLOS One. 2017;12(7):e0181015. doi:10.1371/journal.pone.0181015.
  • Yang L, Zhang X, Peng W, et al. MicroRNA-155-induced T lymphocyte subgroup drifting in IgA nephropathy. Int Urol Nephrol 2017;49(2):353–361. doi:10.1007/s11255-016-1444-3.
  • Li X, Luo F, Li J, et al. MiR-183 delivery attenuates murine lupus nephritis-related injuries via targeting mTOR. Scand J Immunol 2019;90(5):e12810. doi:10.1111/sji.12810.
  • Xu BY, Meng SJ, Shi SF, et al. MicroRNA-21-5p participates in IgA nephropathy by driving T helper cell polarization. J Nephrol 2020;33(3):551–560. doi:10.1007/s40620-019-00682-3.
  • Rutman AK, Negi S, Saberi N, et al. Extracellular vesicles from kidney allografts express miR-218-5p and alter Th17/Treg ratios. Front Immunol 2022;13:784374. doi:10.3389/fimmu.2022.784374.
  • Huang J, Xu X, Wang X, et al. MicroRNA-590-3p inhibits T helper 17 cells and ameliorates inflammation in lupus mice. Immunology 2022;165(2):260–273. doi:10.1111/imm.13434.
  • Han Q, Tong J, Sun Q, et al. The involvement of miR-6615-5p/Smad7 axis and immune imbalance in ammonia-caused inflammatory injury via NF-kappaB pathway in broiler kidneys. Poult Sci 2020;99(11):5378–5388. doi:10.1016/j.psj.2020.08.005.
  • Zhang J, Guo Y, Sun Y, et al. Inhibition of microRNA-448 suppresses CD4(+) T cell inflammatory activation via up-regulating suppressor of cytokine signaling 5 in systemic lupus erythematosus. Biochem Biophys Res Commun 2022;596:88–96. doi:10.1016/j.bbrc.2022.01.097.
  • You G, Cao H, Yan L, et al. MicroRNA-10a-3p mediates Th17/Treg cell balance and improves renal injury by inhibiting REG3A in lupus nephritis. Int Immunopharmacol 2020;88:106891. doi:10.1016/j.intimp.2020.106891.
  • Liu SC, Chen LB, Chen PF, et al. PDCD5 inhibits progression of renal cell carcinoma by promoting T cell immunity: with the involvement of the HDAC3/microRNA-195-5p/SGK1. Clin Epigenetics 2022;14(1):131. doi:10.1186/s13148-022-01336-1.
  • Harrell CR, Jovicic N, Djonov V, et al. Mesenchymal stem cell-derived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases. Cells 2019;8(12):1605. doi:10.3390/cells8121605.
  • Chen S, Shan J, Niu W, et al. Micro RNA-155 inhibitor as a potential therapeutic strategy for the treatment of acute kidney injury (AKI): a nanomedicine perspective. RSC Adv 2018;8(29):15890–15896. doi:10.1039/c7ra13440a.
  • Lv LL, Feng Y, Wu M, et al. Exosomal miRNA-19b-3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury. Cell Death Differ 2020;27(1):210–226. doi:10.1038/s41418-019-0349-y.
  • Bahmani L, Baghi M, Peymani M, et al. The PBX1/miR-141-miR-200a/EGR2/SOCS3 axis; integrative analysis of interaction networks to discover the possible mechanism of MiR-141 and MiR-200a-mediated Th17 cell differentiation. Iran J Biotechnol 2023;21(1):e3211. doi:10.30498/ijb.2022.317078.3211.
  • Zhang L, Sun P, Zhang Y, et al. miR-182-5p inhibits the pathogenic Th17 response in experimental autoimmune uveitis mice via suppressing TAF15. Biochem Biophys Res Commun 2020;529(3):784–792. doi:10.1016/j.bbrc.2020.06.073.
  • Xue Y, Zhang L, Guo R, et al. miR-485 regulates Th17 generation and pathogenesis in experimental autoimmune encephalomyelitis through targeting STAT3. J Neuroimmunol 2023;379:578100. doi:10.1016/j.jneuroim.2023.578100.
  • Murugaiyan G, DA Cunha AP, Ajay AK, et al. MicroRNA-21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis. J Clin Invest 2015;125(3):1069–1080. doi:10.1172/jci74347.
  • Zhang Z, Xue Z, Liu Y, et al. MicroRNA-181c promotes Th17 cell differentiation and mediates experimental autoimmune encephalomyelitis. Brain Behav Immun 2018;70:305–314. doi:10.1016/j.bbi.2018.03.011.
  • Feng R, Cui Z, Liu Z, et al. Upregulated microRNA-132 in T helper 17 cells activates hepatic stellate cells to promote hepatocellular carcinoma cell migration in vitro. Scand J Immunol 2021;93(5):e13007. doi:10.1111/sji.13007.
  • Krebs CF, Paust HJ, Krohn S, et al. Autoimmune renal disease is exacerbated by S1P-receptor-1-dependent intestinal Th17 cell migration to the kidney. Immunity 2016;45(5):1078–1092. doi:10.1016/j.immuni.2016.10.020.
  • Bian J, Liebert A, Bicknell B, et al. Faecal microbiota transplantation and chronic kidney disease. Nutrients 2022;14(12):2528. doi:10.3390/nu14122528.
  • Valiente GR, Munir A, Hart ML, et al. Gut dysbiosis is associated with acceleration of lupus nephritis. Sci Rep 2022;12(1):152. doi:10.1038/s41598-021-03886-5.
  • Li D, Pan Y, Xia X, et al. Bacteroides fragilis alleviates the symptoms of lupus nephritis via regulating CD1d and CD86 expressions in B cells. Eur J Pharmacol 2020;884:173421. doi:10.1016/j.ejphar.2020.173421.
  • Zhou P, Sun X, Zhang Z. Kidney-targeted drug delivery systems. Acta Pharm Sin B 2014;4(1):37–42. doi:10.1016/j.apsb.2013.12.005.
  • Hirota K, Duarte JH, Veldhoen M, et al. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol 2011;12(3):255–263. doi:10.1038/ni.1993.
  • Ochi M, Toyama T, Ando M, et al. A case of secondary IgA nephropathy accompanied by psoriasis treated with secukinumab. CEN Case Rep 2019;8(3):200–204. doi:10.1007/s13730-019-00393-5.
  • Ikuma D, Oguro M, Hoshino J, et al. Efficacy of secukinumab for plaque psoriasis in a patient on hemodialysis. CEN Case Rep 2020;9(1):55–58. doi:10.1007/s13730-019-00426-z.
  • Pizzatti L, Mugheddu C, Sanna S, et al. Erythrodermic psoriasis in a dialyzed patient successfully treated with secukinumab. Dermatol Ther 2020;33(3):e13348. doi:10.1111/dth.13348.
  • Costa R, Antunes P, Salvador P, et al. Secukinumab on refractory lupus nephritis. Cureus 2021;13(8):e17198. doi:10.7759/cureus.17198.
  • Sandys V, Moloney B, Lane L, et al. Granulomatous interstitial nephritis secondary to adalimumab therapy. Clin Kidney J 2018;11(2):219–221. doi:10.1093/ckj/sfx104.
  • Babino G, Fulgione E, Giorgio CM, et al. Efficacy and safety of secukinumab in a psoriatic patient affected by comorbid metabolic disorders. Dermatol Ther 2019;32(3):e12858. doi:10.1111/dth.12858.
  • Hesius E, Bunthof K, Steenbergen E, et al. Monoclonal gammopathy of renal significance presenting with cryoglobulinaemia type I associated severe thrombotic microangiopathy. Clin Kidney J 2022;15(7):1425–1428. doi:10.1093/ckj/sfac078.
  • Koike Y, Fujiki Y, Higuchi M, et al. An interleukin-17 inhibitor successfully treated a complicated psoriasis and psoriatic arthritis patient with hepatitis B virus infection and end-stage kidney disease on hemodialysis. JAAD Case Rep 2019;5(2):150–152. doi:10.1016/j.jdcr.2018.11.016.
  • DI Altobrando A, Lacava R, Patrizi A, et al. Use of anti-IL 17A for psoriasis is not necessarily contraindicated in organ transplantation patients. Eur J Dermatol 2020;30(3):311–313. doi:10.1684/ejd.2020.3776.
  • Liles JE, Flanigan K, Davis LS. Association of IL-17 inhibitor and SGLT2 inhibitor with Candida Pyelonephritis. Am J Med 2021;134(11):e561–e2. doi:10.1016/j.amjmed.2021.05.033.
  • Amoruso GF, Nisticò SP, Iannone L, et al. Ixekizumab may improve renal function in psoriasis. Healthcare 2021;9(5):543. doi:10.3390/healthcare9050543.
  • Ishibashi M, Shiiyama R. A case of psoriasis vulgaris treated with brodalumab in a hemodialysis patient with end-stage renal disease due to diabetic nephropathy. Case Rep Dermatol Med 2020;2020:3863152. doi:10.1155/2020/3863152.
  • Hueber W, Sands BE, Lewitzky S, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 2012;61(12):1693–1700. doi:10.1136/gutjnl-2011-301668.
  • Wang J, Zou JX, Xue X, et al. ROR-gamma drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer. Nat Med 2016;22(5):488–496. doi:10.1038/nm.4070.
  • Hu X, Liu X, Moisan J, et al. Synthetic RORgamma agonists regulate multiple pathways to enhance antitumor immunity. Oncoimmunology 2016;5(12):e1254854. doi:10.1080/2162402x.2016.1254854.
  • Wang R, Campbell S, Amir M, et al. Genetic and pharmacological inhibition of the nuclear receptor RORalpha regulates TH17 driven inflammatory disorders. Nat Commun 2021;12(1):76. doi:10.1038/s41467-020-20385-9.
  • He J, Zhang R, Shao M, et al. Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 2020;79(1):141–149. doi:10.1136/annrheumdis-2019-215396.
  • He J, Zhang X, Wei Y, et al. Low-dose interleukin-2 treatment selectively modulates CD4(+) T cell subsets in patients with systemic lupus erythematosus. Nat Med 2016;22(9):991–993. doi:10.1038/nm.4148.
  • Brede KM, Schmid J, Steinmetz OM, et al. Neutralization of IL-6 inhibits formation of autoreactive TH17 cells but does not prevent loss of renal function in experimental autoimmune glomerulonephritis. Immunol Lett. 2021;236:51–60. doi:10.1016/j.imlet.2021.05.002.
  • Scheller J, Garbers C, Rose-John S. Interleukin-6: from basic biology to selective blockade of pro- inflammatory activities. Semin Immunol 2014;26(1):2–12. doi:10.1016/j.smim.2013.11.002.
  • Tyagi AM, Darby TM, Hsu E, et al. The gut microbiota is a transmissible determinant of skeletal maturation. Elife. 2021;10:e64237. doi:10.7554/eLife.64237.
  • Lauriero G, Abbad L, Vacca M, et al. Fecal microbiota transplantation modulates renal phenotype in the humanized mouse model of IgA nephropathy. Front Immunol 2021;12:694787. doi:10.3389/fimmu.2021.694787.
  • Beurel E, Lowell JA. Th17 cells in depression. Brain Behav Immun 2018;69:28–34. doi:10.1016/j.bbi.2017.08.001.
  • Zhang D, Jin W, Wu R, et al. High glucose intake exacerbates autoimmunity through reactive-oxygen- species-mediated TGF-beta cytokine activation. Immunity 2019;51(4):671–681.e5. doi:10.1016/j.immuni.2019.08.001.
  • Maggio R, Viscomi C, Andreozzi P, et al. Normocaloric low cholesterol diet modulates Th17/Treg balance in patients with chronic hepatitis C virus infection. PLOS One 2014;9(12):e112346. doi:10.1371/journal.pone.0112346.
  • Cignarella F, Cantoni C, Ghezzi L, et al. Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota. Cell Metab 2018;27(6):1222–1235.e6. doi:10.1016/j.cmet.2018.05.006.
  • Corneth OBJ, Schaper F, Luk F, et al. Lack of IL-17 receptor A signaling aggravates lymphoproliferation in C57BL/6 lpr mice. Sci Rep 2019;9(1):4032. doi:10.1038/s41598-019-39483-w.

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