T Cell Receptor-Regulated TGF-? 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 ? (TGF-?) signaling was present in naive T cells, and T cell receptor (TCR) engagement reduced TGF-? signaling during T cell activation by downregulating TGF-? type 1 receptor (T?RI) through activation of caspase recruitment domain-containing protein 11 (CARD11) and nuclear factor ?B (NF-?B). TGF-? prevented TCR-mediated T?RI downregulation, but this was abrogated by interleukin-6 (IL-6). Mitigation of TCR-mediated T?RI downregulation through overexpression of T?RI in naive and activated T cells rendered T cells less responsive and suppressed autoimmunity. Naive T cells in autoimmune patients exhibited reduced T?RI expression and increased TCR-driven proliferation compared to healthy subjects. Thus, TCR-mediated regulation of T?RI-TGF-? 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