Hee-Meng Tan, A., Wan Tso, G.H., Zhang, B., Teo, P.-Y., Ou, X., Ng, S.-W., Fah Wong, A.X., Xiang Tan, S.J., Sanny, A., Soo-Yeon Kim, S., Lee, A.P., Xu, S., Lam, K.-P., TACI constrains TH17 pathogenicity and protects against gut inflammation, ISCIENCE (2020), doi: https://doi.org/10.1016/j.isci.2020.101707.
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 TH17 but not TH1 or TH2 differentiation. Frequencies and numbers of TH17 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 TH17 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 TH17 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 TH17-promoting transcription factors NFAT, IRF4, c-MAF, and JUNB. Taken together, these findings reveal an important role of TACI in constraining TH17 pathogenicity and protecting against gut disease.
This research was supported by Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore (A∗STAR).