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.
Abstract:
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.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
This research was supported by Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore (A∗STAR).