LAUSR

ABSTRACT The feature of pulmonary sarcoidosis is characterized by a Th1/Th17/regulatory T cells (Tregs) ‐driven inflammatory process in lung, resulting in noncaseating granulomas containing CD4+ T cells. Tregs increase in both lung and peripheral blood, with damaged immunoregulatory function. The current study investigated the effects of IL33 or anti‐IL23 antibody on restoring the homeostasis and functions of Tregs in mycobacterial superoxide dismutase A (SodA)‐induced pulmonary sarcoidosis. IL33 or anti‐IL23 antibody was administered to mice with late‐stage pulmonary sarcoidosis. The levels of Th1/Th17/Tregs and Tregs' suppressive functions were detected by fluorescence activated cell sorting (FACS) analysis or qPCR. The expressions of key proteins in PI3K/Akt/mTOR and TGF‐&bgr;/Smad2/Smad3 signaling pathways were tested by western blot. IL33 administration was associated with the rebalance of Th1/Th2 and Tregs, as well as a superior suppressor activity of Tregs on effector T cells in sarcoidosis, probably through increasing ST2 expressions on Tregs, along with the suppression of PI3K/Akt/mTOR and TGF‐&bgr;/Smad2/Smad3 signaling pathways. Small dose of anti‐IL23 antibody independently improved Th1/Th2 bias, but had limited effects on the homeostasis and ST2 expressions on Tregs. These results suggested a major anti‐inflammatory ability of IL33 to ameliorate the disturbance of Th1/Th2 and Tregs in pulmonary sarcoidosis, and provided rationales for further strategies of targeting the IL33/ST2 signals in the treatment of pulmonary sarcoidosis. HighlightsDisturbance of Tregs in SodA‐induced sarcoidosis was ameliorated by IL33.Tregs' function may be sustained through IL33/ST2 regulation.PI3K/Akt pathway was suppressed along with the sustained Tregs' function.