T Cell Receptor-Regulated TGF-β Type I Receptor Expression Determines T Cell Quiescence and Activation.
It is unclear how quiescence is enforced in naive T cells, but activation by foreign antigens and self-antigens is allowed, despite the presence of inhibitory signals. We showed that active transforming growth factor β (TGF-β) signaling was present in naive T cells, and T cell receptor (TCR) engagement reduced TGF-β signaling during T cell activation by downregulating TGF-β type 1 receptor (TβRI) through activation of caspase recruitment domain-containing protein 11 (CARD11) and nuclear factor κB (NF-κB). TGF-β prevented TCR-mediated TβRI downregulation, but this was abrogated by interleukin-6 (IL-6). Mitigation of TCR-mediated TβRI downregulation through overexpression of TβRI in naive and activated T cells rendered T cells less responsive and suppressed autoimmunity. Naive T cells in autoimmune patients exhibited reduced TβRI expression and increased TCR-driven proliferation compared to healthy subjects. Thus, TCR-mediated regulation of TβRI-TGF-β signaling acts as a crucial criterion to determine T cell quiescence and activation.
['Tu|Eric|E|', 'Chia|Cheryl P Z|CPZ|', 'Chen|Weiwei|W|', 'Zhang|Dunfang|D|', 'Park|Sang A|SA|', 'Jin|Wenwen|W|', 'Wang|Dandan|D|', 'Alegre|Maria-Luisa|ML|', 'Zhang|Ying E|YE|', 'Sun|Lingyun|L|', 'Chen|WanJun|W|']
D000818:Animals D015551:Autoimmunity D053468:CARD Signaling Adaptor Proteins D015496:CD4-Positive T-Lymphocytes D002460:Cell Line D049109:Cell Proliferation D003092:Colitis D004195:Disease Models, Animal D015536:Down-Regulation D006162:Guanylate Cyclase D057809:HEK293 Cells D006801:Humans D015850:Interleukin-6 D008180:Lupus Erythematosus, Systemic D008213:Lymphocyte Activation D051379:Mice D008807:Mice, Inbred BALB C D008810:Mice, Inbred C57BL D018345:Mice, Knockout D016328:NF-kappa B D000077293:Receptor, Transforming Growth Factor-beta Type I D011948:Receptors, Antigen, T-Cell D015398:Signal Transduction D053773:Transforming Growth Factor beta1
TGF-β T cell quiescence signaling CARD11 IL-6 autoimmunity NF-kB T cell activation TCR signaling receptor I downregulation