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- Title
Homotypic NK cell-to-cell communication controls cytokine responsiveness of innate immune NK cells.
- Authors
Tae-Jin Kim; Miju Kim; Hye Mi Kim; Seon Ah Lim; Eun-Ok Kim; Kwanghee Kim; Kwang Hoon Song; Jiyoung Kim; Kumar, Vinay; Yee, Cassian; Junsang Doh; Kyung-Mi Lee
- Abstract
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, 'orphan' 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.
- Subjects
CELL communication; KILLER cells; CYTOKINES; NATURAL immunity; CELL proliferation
- Publication
Scientific Reports, 2014, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep07157