Th17 cell pathogenicity in autoimmune disease

Abstract

T helper 17 (Th17) cells have been implicated in numerous inflammatory autoimmune diseases. Clinical benefits from targeting Th17 cell-related cytokines, such as IL-17 and IL-23, highlight how knowledge of Th17 cell development and effector function can be translated into treatments for inflammatory disease. Here we discuss the pathogenic roles of Th17 cells in autoimmune diseases such as multiple sclerosis, inflammatory bowel disease and psoriasis, with emphasis on the cytokines, transcriptional regulators and metabolites that influence Th17 cell differentiation and pathogenicity. Moreover, we address how intestinal environments and physiological responses affect Th17 cells in autoimmune diseases. We also examine current and emerging therapeutic strategies aimed at regulating Th17 cell-driven inflammation to mitigate autoimmune diseases.

Fig. 1. Therapeutic approaches targeting Th17 cell-driven inflammation.

a SMIs can target JAK isoforms or transcription factors such as RORγt and RORα to suppress Th17 cells. ADC can promote the target-specific delivery of SMIs. b Blockade of cytokines or cytokine receptors using antibodies or peptides can inhibit Th17 cell-mediated inflammation. c Inhibitory antibodies targeting integrins or adhesion molecules can inhibit the infiltration of Th17 cells into the site of inflammation. d CAR-T cells can directly kill pathogenic cells in Th17 cell-driven inflammation. CAR-T_reg cells can suppress inflammation driven by Th17 cells.