Table 1: Preclinical mouse models showing a role for Th17 cells and the IL-17 pathway in autoimmunity.

DiseaseModelRole of Th17Reference

Rheumatoid arthritisCollagen-induced arthritis (CIA)IL-23 (p19 subunit) KO mice have less Th17 cells and reduced disease severity[35]
Collagen-induced arthritis (CIA)IL-17A KO mice have reduced disease incidence and severity [36]
IL-6R subunit gp130 (Y759F) mutationEnforced IL-6 expression enhances disease progression in an IL-17A-dependent manner[37]
SKG-dominant active ZAP70 mutantIL-17A KO mice are resistant to arthritis [39]
HTLV-I Tg miceIL-17A KO mice are resistant to arthritis[41]

Inflammatory Bowel diseaseAdoptive transfer of CD4+CD45RBhi cells to lymphopenic miceIL-17A KO CD4+ T cells accelerated T-cell-mediated intestinal damage [42]
Adoptive transfer of CD4+CD45RBhi cells to lymphopenic miceIL-17A, IL-17F, or IL-22 KO T-cells-induced colitis equally compared to WT [43]
Dextran sodium sulfate (DSS)IL-17F KO or IL-17A KO or mice treated with an anti-IL-17A antibody showed severe weight loss and colonic epithelial damage [44, 45]
Dextran sodium sulfate (DSS)IL-17A KO showed substantially reduced colitis based on both clinical score and mortality[46]

Topical application of imiquimod (IMQ)Dermatitis is blocked in IL-23R KO and IL-17R KO mice[53]
PsoriasisIL-23 injectionIL-6-dependent accumulation of Th17 cells in psoriatic skin, dermatitis was greatly reduced in IL-22 KO or IL-17A KO mice [55, 56]
K5.Stat3C transgenic mice Constitutively express activated Stat3 within keratinocytes promotes Th17 cells, and anti-IL-23 was shown to block epidermal hyperplasia; however, anti-IL-17 had only partial effect[57]

Type 1 diabetesRIP-OVA mice (mice expressing OVA peptide in pancreatic beta islet cells )IL-17 producing CD8+ T cells (Tc17) cause diabetes in an IL-17A- and IL-17F-dependent manner when adoptively transferred to RIP-OVA mice[59]
Nonobese diabetes (NOD)Anti-IL-17A antibodies inhibit diabetes during the effector phase of disease (at 10 weeks of age) but not during the initiation of disease (mice less than 5 weeks of age)[60]