title: Homotypic NK cell-to-cell communication controls cytokine responsiveness of innate immune NK cells.
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.
authors.affiliation: Global Research Lab, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-713, Korea.
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: 1] School of Interdisciplinary Bioscience and Bioengineering (I-Bio), Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, Korea [2] Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, Korea.
authors.forename: Miju
authors.initials: M
authors.lastname: Kim
authors.affiliation: Division of Integrative Biosciences and Biotechnology (IBB), Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, Korea.
authors.forename: Hye Mi
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Global Research Lab, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-713, Korea.
authors.forename: Seon Ah
authors.initials: SA
authors.lastname: Lim
authors.affiliation: Global Research Lab, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-713, Korea.
authors.forename: Eun-Ok
authors.initials: EO
authors.lastname: Kim
authors.affiliation: 1] Global Research Lab, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-713, Korea [2] Departments of Melanoma Medical Oncology and Immunology, MD Anderson Cancer Center Houston, TX 77054, USA.
authors.forename: Kwanghee
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, Korea.
authors.forename: Kwang Hoon
authors.initials: KH
authors.lastname: Song
authors.affiliation: Global Research Lab, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-713, Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Vinay
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Departments of Melanoma Medical Oncology and Immunology, MD Anderson Cancer Center Houston, TX 77054, USA.
authors.forename: Cassian
authors.initials: C
authors.lastname: Yee
authors.affiliation: 1] School of Interdisciplinary Bioscience and Bioengineering (I-Bio), Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, Korea [2] Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, Korea.
authors.forename: Junsang
authors.initials: J
authors.lastname: Doh
authors.affiliation: 1] Global Research Lab, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-713, Korea [2] Departments of Melanoma Medical Oncology and Immunology, MD Anderson Cancer Center Houston, TX 77054, USA.
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Lee
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D002452:Cell Count; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D060833:Cellular Microenvironment / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016207:Cytokines