Th17 cells play a critical role in both tissue homeostasis and inflammation during clearance of infections as well as autoimmune and inflammatory disorders. Despite numerous efforts to distinguish the homeostatic and inflammatory roles of Th17 cells, the mechanism underlying the divergent functions of inflammatory Th17 cells remains poorly understood. In this study, we demonstrate that the inflammatory Th17 cells involved in autoimmune colitis and those activated during colitogenic infection are distinguishable populations characterized by their differential responses to the pharmacological molecule, clofazimine (CLF). Unlike existing Th17 inhibitors, CLF selectively inhibits proautoimmune Th17 cells while preserving the functional state of infection-elicited Th17 cells partially by reducing the enzyme ALDH1L2. Overall, our study identifies two distinct subsets within the inflammatory Th17 compartment with distinct regulatory mechanisms. Furthermore, we highlight the feasibility to develop disease-promoting Th17 selective inhibitor for treating autoimmune diseases.
© 2023 Bouch et al.