| First Author | Pan Y | Year | 2020 |
| Journal | Eur J Immunol | Volume | 50 |
| Issue | 2 | Pages | 192-204 |
| PubMed ID | 31710099 | Mgi Jnum | J:285309 |
| Mgi Id | MGI:6390618 | Doi | 10.1002/eji.201948289 |
| Citation | Pan Y, et al. (2020) Graded diacylglycerol kinases alpha and zeta activities ensure mucosal-associated invariant T-cell development in mice. Eur J Immunol 50(2):192-204 |
| abstractText | Mucosal-associated invariant T (MAIT) cells participate in both protective immunity and pathogenesis of diseases. Most murine MAIT cells express an invariant TCRValpha19-Jalpha33 (iValpha19) TCR, which triggers signals crucial for their development. However, signal pathways downstream of the iValpha19TCR and their regulation in MAIT cells are unknown. Diacylglycerol (DAG) is a critical second messenger that relays the TCR signal to multiple downstream signaling cascades. DAG is terminated by DAG kinase (DGK)-mediated phosphorylation and conversion to phosphatidic acid. We have demonstrated here that downregulation of DAG caused by enhanced DGK activity impairs late-stage MAIT cell maturation in both thymus and spleen. Moreover, deficiency of DGKzeta but not DGKalpha by itself causes modest decreases in MAIT cells, and deficiency of both DGKalpha and zeta results in severe reductions of MAIT cells in an autonomous manner. Our studies have revealed that DAG signaling is not only critical but also must be tightly regulated by DGKs for MAIT cell development and that both DGKalpha and, more prominently, DGKzeta contribute to the overall DGK activity for MAIT cell development. |
