TACI Constrains T17 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 by cytokines responsible for T17 but not T1 or T2 differentiation. Frequencies and numbers of T17 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 T17 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 T17 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 T17-promoting transcription factors NFAT, IRF4, c-MAF, and JUNB. Taken together, these findings reveal an important role of TACI in constraining T17 pathogenicity and protecting against gut disease.