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dc.contributor.authorTan, Andy Hee-Mengen_US
dc.contributor.authorTso, Gloria Hoi Wanen_US
dc.contributor.authorZhang, Biyanen_US
dc.contributor.authorTeo, Pei-Yunen_US
dc.contributor.authorOu, Xijunen_US
dc.contributor.authorNg, Sze-Waien_US
dc.contributor.authorWong, Alex Xing Fahen_US
dc.contributor.authorTan, Sean Jing Xiangen_US
dc.contributor.authorSanny, Arleenen_US
dc.contributor.authorKim, Susana Soo-Yeonen_US
dc.contributor.authorLee, Alison P.en_US
dc.contributor.authorXu, Shenglien_US
dc.contributor.authorLam, Kong-Pengen_US
dc.identifier.citationTan, 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.2020.101707en_US
dc.description.abstractTACI (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.en_US
dc.description.sponsorshipAgency for Science, Technology and Research (A*STAR)en_US
dc.rights© 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (
dc.subjectScience::Biological sciencesen_US
dc.titleTACI constrains TH17 pathogenicity and protects against gut inflammationen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.organizationBioprocessing Technology Institute, A*STARen_US
dc.contributor.organizationSingapore Immunology Network, A*STARen_US
dc.description.versionPublished versionen_US
dc.subject.keywordsTransmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactoren_US
dc.description.acknowledgementWe thank staff of the Biological Resource Centre (BRC) for care and maintenance of mice and members of the laboratory for insightful discussions. The Advanced Molecular Pathology Laboratory (AMPL) of the Institute of Molecular and Cell Biology assisted in the preparation and histological staining of colon samples. This research was supported by Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore (A∗STAR).en_US
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