Homotypic NK cell-to-cell communication controls cytokine responsiveness of innate immune NK cells

作者：Kim Tae Jin; Kim Miju; Kim Hye Mi; Lim Seon Ah; Kim Eun Ok; Kim Kwanghee; Song Kwang Hoon; Kim Jiyoung; Kumar Vinay; Yee Cassian; Doh Junsang^*; Lee Kyung Mi

来源：Scientific Reports, 2014, 4(1): 7157.

DOI：10.1038/srep07157

While stationary organ cells are in continuous contact with neighboring cells, immune cells circulate throughout the body without an apparent requirement for cell-cell contact to persist in vivo. This study challenges current convention by demonstrating, both in vitro and in vivo, that innate immune NK cells can engage in homotypic NK-to-NK cell interactions for optimal survival, activation, and proliferation. Using a specialized cell-laden microwell approach, we discover that NK cells experiencing constant NK-to-NK contact exhibit a synergistic increase in activation status, cell proliferation, and anti-tumor function in response to IL-2 or IL-15. This effect is dependent on 2B4/CD48 ligation and an active cytoskeleton, resulting in amplification of IL-2 receptor signaling, enhanced CD122/CD132 colocalization, CD25 upregulation, and Stat3 activation. Conversely, %26apos;orphan%26apos; NK cells demonstrate no such synergy and fail to persist. Therefore, our data uncover the existence of homotypic cell-to-cell communication among mobile innate lymphocytes, which promotes functional synergy within the cytokine-rich microenvironment.

• 出版日期2014-12-5