Important role for NKp30 in synapse formation and activation of NK cells

Abstract

Natural killer (NK) cells play an important role in host defense against viral infections and tumor cells. NK cells require contact with target cells and must subsequently form an NK cell immunological synapse (NKIS). The NKIS represents the interface formed between NK cells and their target cells via receptor recognition and adhesion molecule binding, and it is essential for NK cell cytotoxicity, which is mediated through degranulation and release of cytolytic enzymes. In this study, NKp30-mediated signaling and the role of NKp30 in the formation of the NKIS were investigated. The results from confocal microscopy studies showed that the activating receptor, NKp30, and the adhesion molecule, LFA-1 (CD11a), accumulated at the interface between NK92 cells, which are a human NK cell line, and HeLa cells, which are a human tumor cell line (NK92-HeLa). Blockade of NKp30 inhibited NK cell degranulation, cytotoxicity and cytokine secretion but did not affect the conjugation between NK and target cells. Additionally, ligation with HeLa cells activated the Erk1/2 signaling pathway in NK92 cells, and blockade of NKp30 decreased the phosphorylation of Erk1/2. Therefore, NKp30 is a triggering receptor downstream of adhesion and plays an important role in NK cell activation, degranulation and cytotoxicity.