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

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

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17 Citations (Scopus)

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.

Original languageEnglish
Article number7157
JournalScientific reports
Volume4
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • General

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    Kim, T. J., Kim, M., Kim, H. M., Lim, S. A., Kim, E. O., Kim, K., Song, K. H., Kim, J., Kumar, V., Yee, C., Doh, J., & Lee, K. M. (2014). Homotypic NK cell-to-cell communication controls cytokine responsiveness of innate immune NK cells. Scientific reports, 4, [7157]. https://doi.org/10.1038/srep07157