Spinal cord injury (SCI) is a severe central nervous system injury that often causes permanent motor and sensory function loss. In recent years, increasing studies have focused on the role of the immune system in SCI, especially that of interleukin‑17 (IL‑17), a key cytokine. Previous research has shown that IL‑17 plays important roles in the inflammatory response and tissue repair following SCI, suggesting its potential as a therapeutic target. This review aims to explore the research progress regarding the role of IL‑17 in spinal cord injury and its potential therapeutic applications.

Li Quanneng, Zhang Zhiwei. Research Progress on the Role of IL-17 in Spinal Cord Injury. Frontiers in Medical Science Research (2026), Vol. 8, Issue 3: 18-23. https://doi.org/10.25236/FMSR.2026.080303.

[1] Yao Z, Painter SL, Fanslow WC, Ulrich D, Macduff BM, Spriggs MK, Armitage RJ: Human IL-17: a novel cytokine derived from T cells. J Immunol 1995, 155(12):5483–5486.

[2] Rouvier E, Luciani MF, Mattéi MG, Denizot F, Golstein P: CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol 1993, 150(12):5445–5456.

[3] Albanesi C, Cavani A, Girolomoni G: IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-gamma and TNF-alpha. J Immunol 1999, 162(1):494–502.

[4] Fossiez F, Djossou O, Chomarat P, Flores-Romo L, Ait-Yahia S, Maat C, Pin JJ, Garrone P, Garcia E, Saeland S et al: T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 1996, 183(6):2593–2603.

[5] Faour WH, Mancini A, He QW, Di Battista JA: T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade: role of distal sequences in the 3'-untranslated region of COX-2 mRNA. J Biol Chem 2003, 278(29):26897–26907.

[6] Amatya N, Garg AV, Gaffen SL: IL-17 Signaling: The Yin and the Yang. Trends Immunol 2017, 38(5):310–322.

[7] Li Q, Li X, Lou Y, Xing Y, Yan W, Chen Y, Hu G, Song X, Liu Z, Yang T et al: The IL17REL gene encodes a decoy receptor of IL-17 family cytokines to control gut inflammation. Nat Immunol 2026, 27(2):225–235.

[8] Wang Y, Yu HM, He Y, Cai JC, Tian Y, Chen XY, Wu QY, Yuan TF, Xie AM, Guo Y et al: IL-17A in the hippocampus regulates despair-like behaviors via inhibitory synaptic transmission. Acta Pharmacol Sin 2026.

[9] 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.

[10] Chang SH, Dong C: A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses. Cell Res 2007, 17(5):435–440.

[11] Kolls JK, Lindén A: Interleukin-17 family members and inflammation. Immunity 2004, 21(4):467–476.

[12] Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT: 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.

[13] Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q et al: A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005, 6(11):1133–1141.

[14] Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT: Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 2006, 441(7090):231–234.

[15] Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK: Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006, 441(7090):235–238.

[16] Stockinger B, Veldhoen M, Martin B: Th17 T cells: linking innate and adaptive immunity. Semin Immunol 2007, 19(6):353–361.

[17] Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ: IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005, 201(2):233–240.

[18] Sutton C, Brereton C, Keogh B, Mills KH, Lavelle EC: A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J Exp Med 2006, 203(7):1685–1691.

[19] Lalor SJ, Dungan LS, Sutton CE, Basdeo SA, Fletcher JM, Mills KH: Caspase-1-processed cytokines IL-1beta and IL-18 promote IL-17 production by gammadelta and CD4 T cells that mediate autoimmunity. J Immunol 2011, 186(10):5738–5748.

[20] Conti HR, Peterson AC, Brane L, Huppler AR, Hernández-Santos N, Whibley N, Garg AV, Simpson-Abelson MR, Gibson GA, Mamo AJ et al: Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections. J Exp Med 2014, 211(10):2075–2084.

[21] Marks BR, Nowyhed HN, Choi JY, Poholek AC, Odegard JM, Flavell RA, Craft J: Thymic self-reactivity selects natural interleukin 17-producing T cells that can regulate peripheral inflammation. Nat Immunol 2009, 10(10):1125–1132.

[22] Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH: Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity 2009, 31(2):331–341.

[23] Martin B, Hirota K, Cua DJ, Stockinger B, Veldhoen M: Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. Immunity 2009, 31(2):321–330.

[24] Edwards SC, Sutton CE, Ladell K, Grant EJ, McLaren JE, Roche F, Dash P, Apiwattanakul N, Awad W, Miners KL et al: A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans. J Exp Med 2020, 217(5).

[25] Wang B, Zhao CH, Sun G, Zhang ZW, Qian BM, Zhu YF, Cai MY, Pandey S, Zhao D, Wang YW et al: IL-17 induces the proliferation and migration of glioma cells through the activation of PI3K/Akt1/NF-κB-p65. Cancer Lett 2019, 447:93–104.

[26] Guo B, Zuo Z, Di X, Huang Y, Gong G, Xu B, Wang L, Zhang X, Liang Z, Hou Y et al: Salidroside attenuates HALI via IL-17A-mediated ferroptosis of alveolar epithelial cells by regulating Act1-TRAF6-p38 MAPK pathway. Cell Commun Signal 2022, 20(1):183.

[27] Yang YF, Lee YC, Lo S, Chung YN, Hsieh YC, Chiu WC, Yuan SF: A positive feedback loop of IL-17B-IL-17RB activates ERK/β-catenin to promote lung cancer metastasis. Cancer Lett 2018, 422:44–55.

[28] Hu L, Liu R, Zhang L: Advance in bone destruction participated by JAK/STAT in rheumatoid arthritis and therapeutic effect of JAK/STAT inhibitors. Int Immunopharmacol 2022, 111:109095.

[29] Liang F, Xu Z, Ding L, Zhu Z, Chen M, Shu H, Huang X, Su Z, Wang X, Xiao Y et al: Biomass fuel induces neuroinflammation and neurodegeneration via the astrocyte-microglia IL-17A/IL-17RA pathway. J Hazard Mater 2025, 494:138569.

[30] Hill F, Kim CF, Gorrie CA, Moalem-Taylor G: Interleukin-17 deficiency improves locomotor recovery and tissue sparing after spinal cord contusion injury in mice. Neurosci Lett 2011, 487(3):363–367.

[31] Ma X, Reynolds SL, Baker BJ, Li X, Benveniste EN, Qin H: IL-17 enhancement of the IL-6 signaling cascade in astrocytes. J Immunol 2010, 184(9):4898–4906.

[32] Meares GP, Ma X, Qin H, Benveniste EN: Regulation of CCL20 expression in astrocytes by IL-6 and IL-17. Glia 2012, 60(5):771–781.

[33] You T, Bi Y, Li J, Zhang M, Chen X, Zhang K, Li J: IL-17 induces reactive astrocytes and up-regulation of vascular endothelial growth factor (VEGF) through JAK/STAT signaling. Sci Rep 2017, 7:41779.

[34] He J, Zhao J, Peng X, Shi X, Zong S, Zeng G: Molecular Mechanism of MiR-136-5p Targeting NF-κB/A20 in the IL-17-Mediated Inflammatory Response after Spinal Cord Injury. Cell Physiol Biochem 2017, 44(3):1224–1241.

[35] Yi J, Wang D, Niu X, Hu J, Zhou Y, Li Z: MicroRNA-155 Deficiency Suppresses Th17 Cell Differentiation and Improves Locomotor Recovery after Spinal Cord Injury. Scand J Immunol 2015, 81(5):284–290.

[36] Zong S, Zeng G, Fang Y, Peng J, Tao Y, Li K, Zhao J: The role of IL-17 promotes spinal cord neuroinflammation via activation of the transcription factor STAT3 after spinal cord injury in the rat. Mediators Inflamm 2014, 2014:786947.

[37] Miyajima H, Itokazu T, Tanabe S, Yamashita T: Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice. Cell Death Dis 2021, 12(8):766.

[38] Li Z, Li K, Zhu L, Kan Q, Yan Y, Kumar P, Xu H, Rostami A, Zhang GX: Inhibitory effect of IL-17 on neural stem cell proliferation and neural cell differentiation. BMC Immunol 2013, 14:20.

[39] Liu M, Sun Z, Liang F, Yao R, Yang L, Nan D, Yang J, Su Q, Liu X: IL-17 + γδT cell: a new target in hyperbaric oxygen treatment reducing spinal cord injury. J Transl Med 2025, 23(1):1124.