Tight regulation of diacylglycerol-mediated signaling is critical for proper invariant NKT cell development.

Published

Journal Article

Type I NKT cells, or invariant NKT (iNKT) cells, express a semi-invariant TCR characterized by its unique Vα14-Jα18 usage (iVα14TCR). Upon interaction with glycolipid/CD1d complexes, the iVα14TCRs 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-IκB kinase (IKK)α/β-NF-κB 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 α and ζ causes severe defects in iNKT development, coincident with enhanced IKK-NF-κB and Ras-Erk1/2 activation. Moreover, constitutive IKKβ 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.

Full Text

Duke Authors

Cited Authors

  • Shen, S; Wu, J; Srivatsan, S; Gorentla, BK; Shin, J; Xu, L; Zhong, X-P

Published Date

  • September 1, 2011

Published In

Volume / Issue

  • 187 / 5

Start / End Page

  • 2122 - 2129

PubMed ID

  • 21775687

Pubmed Central ID

  • 21775687

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1100495

Language

  • eng

Conference Location

  • United States