| First Author | Shen S | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 5 | Pages | 2122-9 |
| PubMed ID | 21775687 | Mgi Jnum | J:179149 |
| Mgi Id | MGI:5301206 | Doi | 10.4049/jimmunol.1100495 |
| Citation | Shen S, et al. (2011) Tight regulation of diacylglycerol-mediated signaling is critical for proper invariant NKT cell development. J Immunol 187(5):2122-9 |
| abstractText | Type I NKT cells, or invariant NKT (iNKT) cells, express a semi-invariant TCR characterized by its unique Valpha14-Jalpha18 usage (iValpha14TCR). Upon interaction with glycolipid/CD1d complexes, the iValpha14TCRs transduce signals that are essential for iNKT selection and maturation. However, it remains unclear how these signals are regulated and how important such regulations are during iNKT development. Diacylglycerol (DAG) is an essential second messenger downstream of the TCR that activates the protein kinase C-IkappaB kinase (IKK)alpha/beta-NF-kappaB pathway, known to be crucial for iNKT development, as well as the RasGRP1-Ras-Erk1/2 pathway in T cells. DAG kinases play an important role in controlling intracellular DAG concentration and thereby negatively regulate DAG signaling. In this article, we report that simultaneous absence of DAG kinase alpha and zeta causes severe defects in iNKT development, coincident with enhanced IKK-NF-kappaB and Ras-Erk1/2 activation. Moreover, constitutive IKKbeta and Ras activities also result in iNKT developmental defects. Thus, DAG-mediated signaling is not only essential but also needs to be tightly regulated for proper iNKT cell development. |
