Distinct roles of interleukin-17 and T helper 17 cells among autoimmune diseases

Interleukin (IL)-17 and T helper 17 (T_H17) cells, a distinct subset of CD4⁺ T cells which promotes the expression of IL-17, mediate host defensive mechanisms to various infections and are involved in the pathogenesis of autoimmune diseases including inflammatory bowel disease (IBD), psoriasis, and rheumatic diseases. IL-17 inhibitors have shown to be effective in psoriasis, but failed to demonstrate response in IBD. Further, clinical trials of IL-17 inhibitors reported some cases of new onset IBD. We aim to discuss the roles of IL-17 and T_H17 cells among autoimmune diseases and the possible immunological mechanisms of new onset IBD in patients undergoing IL-17 inhibitors.

A non-systematic literature review using PubMed/Medline.

IL-17 inhibitors, which either target IL-17 A (secukinumab and ixekizumab) or the IL-17 receptor (brodalumab), have demonstrated clinical benefits in plaque psoriasis, psoriatic arthritis, or axial spondyloarthritis. However, secukinumab and brodalumab have shown no clinical benefit in Crohn's disease and led to frequent serious adverse events including worsening of Crohn's disease. Further, some cases of new onset IBD were reported in clinical trials of IL-17 inhibitors. Consistently, an animal model of colitis has demonstrated that IL-17 can directly inhibit the development of T helper 1 (T_H1) cells and T_H1 cells can induce aggressive colitis in the absence of IL-17 signaling.

IL-17 and T_H17 cells might have protective rather than pro-inflammatory roles in the intestine. IL-17 inhibition may induce inflammation in the intestine by favoring T_H1 pathways, which explain the lack of response to IL-17 inhibitors in IBD.