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|Title:||TACI constrains TH17 pathogenicity and protects against gut inflammation||Authors:||Tan, Andy Hee-Meng
Tso, Gloria Hoi Wan
Wong, Alex Xing Fah
Tan, Sean Jing Xiang
Kim, Susana Soo-Yeon
Lee, Alison P.
|Keywords:||Science::Biological sciences||Issue Date:||2020||Source:||Tan, A. H.-M., Tso, G. H. W., Zhang, B., Teo, P.-Y., Ou, X., Ng, S.-W., . . . Lam, K.-P. (2020). TACI constrains TH17 pathogenicity and protects against gut inflammation. iScience, 23(11), 101707-. doi:10.1016/j.isci.2020.101707||Journal:||iScience||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.||URI:||https://hdl.handle.net/10356/145608||ISSN:||2589-0042||DOI:||10.1016/j.isci.2020.101707||Rights:||© 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
Updated on Feb 4, 2023
Updated on Feb 4, 2023
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