TACI constrains TH17 pathogenicity and protects against gut inflammation

• Main Authors: Tan, Andy Hee-Meng, Tso, Gloria Hoi Wan, Zhang, Biyan, Teo, Pei-Yun, Ou, Xijun, Ng, Sze-Wai, Wong, Alex Xing Fah, Tan, Sean Jing Xiang, Sanny, Arleen, Kim, Susana Soo-Yeon, Lee, Alison P., Xu, Shengli, Lam, Kong-Peng
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Biological sciences; Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor; Immunoglobulin
• Online Access: https://hdl.handle.net/10356/145608
• Institution: Nanyang Technological University

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.