Unknown

Dataset Information

0

T Cell Receptor-Regulated TGF-β Type I Receptor Expression Determines T Cell Quiescence and Activation.


ABSTRACT: 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.

SUBMITTER: Tu E 

PROVIDER: S-EPMC5911925 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

T Cell Receptor-Regulated TGF-β Type I Receptor Expression Determines 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  

Immunity 20180401 4


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 κ  ...[more]

Similar Datasets

| S-EPMC2649123 | biostudies-literature
| S-EPMC8358742 | biostudies-literature
| S-EPMC5173045 | biostudies-literature
| S-EPMC5940262 | biostudies-literature
| S-EPMC8866402 | biostudies-literature
| S-EPMC3195573 | biostudies-literature
| S-EPMC1134864 | biostudies-literature
| S-EPMC2688894 | biostudies-other
| S-EPMC5778452 | biostudies-literature
| S-EPMC5354639 | biostudies-literature