| First Author | Kim TJ | Year | 2014 |
| Journal | Sci Rep | Volume | 4 |
| Pages | 7157 | PubMed ID | 25475707 |
| Mgi Jnum | J:272279 | Mgi Id | MGI:6215392 |
| Doi | 10.1038/srep07157 | Citation | Kim TJ, et al. (2014) Homotypic NK cell-to-cell communication controls cytokine responsiveness of innate immune NK cells. Sci Rep 4:7157 |
| abstractText | 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. |
