NKG2D Triggers Cytotoxicity in Murine Epidermal γδ T Cells Via PI3K-dependent, Syk/ZAP70-independent Signaling Pathway

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2013 Aug 22

PMID 23962808

Citations 16

Authors

Atsuko Ibusuki

Kazuhiro Kawai

Shigeru Yoshida

Youhei Uchida

Ayano Nitahara-Takeuchi

Kimiko Kuroki

Mizuho Kajikawa

Toyoyuki Ose

Katsumi Maenaka

Masanori Kasahara

Takuro Kanekura

Affiliations

Soon will be listed here.

Abstract

Murine epidermal γδ 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.

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