| First Author | Takami M | Year | 2018 |
| Journal | Eur J Immunol | Volume | 48 |
| Issue | 12 | Pages | 1938-1943 |
| PubMed ID | 30298904 | Mgi Jnum | J:269338 |
| Mgi Id | MGI:6259962 | Doi | 10.1002/eji.201847587 |
| Citation | Takami M, et al. (2018) TGF-beta suppresses RasGRP1 expression and supports regulatory T cell resistance against p53-induced CD28-dependent T-cell apoptosis. Eur J Immunol 48(12):1938-1943 |
| abstractText | Thymus-derived regulatory T cells (tTregs) play pivotal roles in immunological self-tolerance and homeostasis. A majority of tTregs are reactive to self-antigens and are constantly exposed to antigenic stimulation. Despite this continuous stimulation, tTreg and conventional T-cell populations remain balanced during homeostasis, but the mechanisms controlling this balance are unknown. We previously reported a form of activation-induced cell death, which is dependent on p53 (p53-induced CD28-dependent T-cell apoptosis, PICA). Under PICA-inducing conditions, tTregs survive while a majority of conventional T cells undergo apoptosis, suggesting there is a survival mechanism that protects tTregs. Here, we report that the expression of RasGRP1 (Ras guanyl-releasing protein 1) is required for PICA, as conventional T cells isolated from RasGRP1-deficient mice become resistant to PICA. After continuous stimulation, tTregs express a substantially lower amount of RasGRP1 compared to conventional T cells. This reduced expression of RasGRP1 is dependent on TGF-beta, as addition of TGF-beta to conventional T cells reduces RasGRP1 expression. Conversely, RasGRP1 expression in tTregs increases when TGF-beta signaling is inhibited. Together, these data show that RasGRP1 expression is repressed in tTregs by TGF-beta signaling and suggests that reduced RasGRP1 expression is critical for tTregs to resist apoptosis caused by continuous antigen exposure. |
