Graded diacylglycerol kinases α and ζ activities ensure mucosal-associated invariant T-cell development in mice
| Autor: | Edwin C K Wan, Wenhai Deng, Jimin Gao, Huishan Tao, Yun Pan, Jinhai Xie, Li Ma, Xiao-Ping Zhong, Zhiming Hu, Lei Li, Yongping Chen, Shimeng Zhang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Diacylglycerol Kinase Cell growth Kinase Immunology T-cell receptor Mucosal associated invariant T cell Biology Mucosal-Associated Invariant T Cells Article Cell biology Diglycerides 03 medical and health sciences Mice 030104 developmental biology 0302 clinical medicine Downregulation and upregulation Second messenger system Immunology and Allergy Animals lipids (amino acids peptides and proteins) Signal transduction 030215 immunology Diacylglycerol kinase Signal Transduction |
| Zdroj: | Eur J Immunol |
| ISSN: | 1521-4141 |
| Popis: | Mucosal-associated invariant T (MAIT) cells participate in both protective immunity and pathogenesis of diseases. Most murine MAIT cells express an invariant TCRVα19-Jα33 (iVα19) TCR, which triggers signals crucial for their development. However, signal pathways downstream of the iVα19TCR 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 DGKζ but not DGKα by itself causes modest decreases in MAIT cells, and deficiency of both DGKα and ζ 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 DGKα and, more prominently, DGKζ contribute to the overall DGK activity for MAIT cell development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text