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This information is current as NKT Cell Development Signaling Is Critical for Proper Invariant Tight Regulation of Diacylglycerol-Mediated
| Content Provider | Semantic Scholar |
|---|---|
| Author | Shen, Shudan Wu, Jinhong Sruti Srivatsan Gorentla, Balachandra K. Shin, Jinwook Zhong, Xiao-Ping |
| Copyright Year | 2011 |
| Abstract | Type I NKT cells, or invariant NKT (iNKT) cells, express a semi-invariant TCR characterized by its unique Va14-Ja18 usage (iVa14TCR). Upon interaction with glycolipid/CD1d complexes, the iVa14TCRs 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 Cu-IkB kinase (IKK)a/b-NF-kB 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 a and z causes severe defects in iNKT development, coincident with enhanced IKK-NF-kB and Ras-Erk1/2 activation. Moreover, constitutive IKKb 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. N atural killer T cells are a subset of rare T cells that bridge innate and adaptive immunity. Despite their rarity, NKT cells play a significant role in the modulation and/or pathogenesis of infectious diseases, allergy, autoimmunity, and cancer, in part due to their ability to secrete a vast array of cytokines within minutes to hours of stimulation (1, 2). Accumulating data support the notion that the NKT population is actually composed of a number of developmentally and functionally distinct subsets (3). The majority of NKT cells express a semi-invariant TCR with a unique Va14-Ja18 chain and a limited Vb repertoire. These cells, called type I NKT cells or invariant NKT (iNKT) cells, recognize glycolipids presented by CD1d and can be readily detected by a-galactosylceramide (a-Galcer)–loaded CD1d-tetramers (CD1d-Tet). Although iNKT cells also arise from double-positive (DP) thymocytes, they differ from conventional ab T (cabT) cells in that they are selected on fellow CD1d-expressing cortical thy-mocytes (as opposed to MHC-bearing thymic epithelial cells) (4, 5). Positively selected iNKT thymocytes downregulate CD24 expression and undergo further maturation marked by sequential upregulation of CD44 and NK1.1 on the cell surface (3). Although terminally mature CD44 + NK1.1 + iNKT thymocytes become long-term residents of the thymus, for reasons yet to be completely understood, CD44 + NK1.1 2 iNKT thymocytes exit to the periphery , where they mature independently and acquire NK1.1 expression (6, 7). Given the … |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/187/5/2122.full.pdf?with-ds=yes |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/early/2011/07/20/jimmunol.1100495.full.pdf |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/187/5/2122.full.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
