| First Author | Ibusuki A | Year | 2014 |
| Journal | J Invest Dermatol | Volume | 134 |
| Issue | 2 | Pages | 396-404 |
| PubMed ID | 23962808 | Mgi Jnum | J:205864 |
| Mgi Id | MGI:5546549 | Doi | 10.1038/jid.2013.353 |
| Citation | Ibusuki A, et al. (2014) NKG2D Triggers Cytotoxicity in Murine Epidermal gammadelta T Cells via PI3K-Dependent, Syk/ZAP70-Independent Signaling Pathway. J Invest Dermatol 134(2):396-404 |
| abstractText | Murine epidermal gammadelta T cells, known as dendritic epidermal T cells (DETCs), survey tissue stress through the invariant T-cell receptor (TCR) and non-clonotypic receptors such as NKG2D. NKG2D signaling via the DAP10-phosphatidylinositol 3-kinase (PI3K) pathway directly stimulates cytotoxicity in natural killer (NK) cells and costimulates CD8(+) T cells to augment TCR signals. In activated murine NK cells, NKG2D signals also via the DAP12-Syk/ZAP70 pathway that triggers both cytotoxicity and cytokine production. It remains controversial whether NKG2D on DETCs is a primary activating receptor or functions only as a costimulatory receptor, and signaling pathways initiated by NKG2D ligation in DETCs have not been analyzed. We show that stimulation of short-term DETC lines with recombinant NKG2D ligands triggers degranulation (exocytosis of cytotoxic granules) via the PI3K-dependent signaling pathway, but does not induce cytokine production or Syk/ZAP70 activation. Coengagement of TCR or Syk/ZAP70 signaling was not crucial for DETC-mediated killing of NKG2D ligand-expressing target cells. Thus, NKG2D can function as a coactivating stress receptor that directly triggers cytotoxicity in DETCs, at least after priming, via the PI3K-dependent, Syk/ZAP70-independent signaling pathway. |
