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

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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
StatePublished - 2014

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future planning (grant NRF-2007-00107 and NRF-2013M3A9D3045719) awarded to K.-M. Lee. and J. Doh is supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea A121177/HI12C1079.


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