TACI Constrains T_H17 Pathogenicity and Protects against Gut Inflammation

TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) plays critical roles in B cells by promoting immunoglobulin class switching and plasma cell survival. However, its expression and function in T cells remain controversial. We show here that TACI expression can be strongly induced in murine CD4⁺ T cells in vitro by cytokines responsible for T_H17 but not T_H1 or T_H2 differentiation. Frequencies and numbers of T_H17 cells were elevated in TACI^{-/ -} compared with wild-type mice as well as among TACI^{-/ -} versus wild-type CD4⁺ T cells in mixed bone marrow chimeras, arguing for a T cell-intrinsic effect in the contribution of TACI deficiency to T_H17 cell accumulation. TACI^{-/ -} mice were more susceptible to severe colitis induced by dextran sodium sulfate or adoptive T cell transfer, suggesting that TACI negatively regulates T_H17 function and limits intestinal inflammation in a cell-autonomous manner. Finally, transcriptomic and biochemical analyses revealed that TACI^{-/ -} CD4⁺ T cells exhibited enhanced activation of T_H17-promoting transcription factors NFAT, IRF4, c-MAF, and JUNB. Taken together, these findings reveal an important role of TACI in constraining T_H17 pathogenicity and protecting against gut disease.