| First Author | Liu X | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 30 | Pages | eabo4577 |
| PubMed ID | 35895826 | Mgi Jnum | J:327610 |
| Mgi Id | MGI:7329493 | Doi | 10.1126/sciadv.abo4577 |
| Citation | Liu X, et al. (2022) SMAD4, activated by the TCR-triggered MEK/ERK signaling pathway, critically regulates CD8(+) T cell cytotoxic function. Sci Adv 8(30):eabo4577 |
| abstractText | Transforming growth factor-beta is well known to restrain cytotoxic T cell responses to maintain self-tolerance and to promote tumor immune evasion. In this study, we have investigated the role of SMAD4, a core component in the TGF-beta signaling pathway, in CD8(+) T cells. Unexpectedly, we found that SMAD4 was critical in promoting CD8(+) T cell function in both tumor and infection models. SMAD4-mediated transcriptional regulation of CD8(+) T cell activation and cytotoxicity was dependent on the T cell receptor (TCR) but not TGF-beta signaling pathway. Following TCR activation, SMAD4 translocated into the nucleus, up-regulated genes encoding TCR signaling components and cytotoxic molecules in CD8(+) T cells and thus reinforced T cell function. Biochemically, SMAD4 was directly phosphorylated by ERK at Ser(367) residue following TCR activation. Our study thus demonstrates a critical yet unexpected role of SMAD4 in promoting CD8(+) T cell-mediated cytotoxic immunity. |
