TACI Constrains T(H)17 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(H)17 but not T(H)1 or T(H)2 differentiation. Frequencies and numbers of T(H)17 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(H)17 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(H)17 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(H)17-promoting transcription factors NFAT, IRF4, c-MAF, and JUNB. Taken together, these findings reveal an important role of TACI in constraining T(H)17 pathogenicity and protecting against gut disease.