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 journalArticle

14 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

Fingerprint

Cell Communication
Natural Killer Cells
Cytokines
Interleukin-15
Interleukin-2 Receptors
Cytoskeleton
Interleukin-2
Ligation
Up-Regulation
Cell Proliferation
Lymphocytes
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Homotypic NK cell-to-cell communication controls cytokine responsiveness of innate immune NK cells. / Kim, Tae Jin; Kim, Miju; Kim, Hye Mi; Lim, Seon Ah; Kim, Eun Ok; Kim, Kwanghee; Song, Kwang Hoon; Kim, Jiyoung; Kumar, Vinay; Yee, Cassian; Doh, Junsang; Lee, Kyung-Mi.

In: Scientific Reports, Vol. 4, 7157, 2014.

Research output: Contribution to journalArticle

Kim, TJ, Kim, M, Kim, HM, Lim, SA, Kim, EO, Kim, K, Song, KH, 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, vol. 4, 7157. https://doi.org/10.1038/srep07157
Kim, Tae Jin ; Kim, Miju ; Kim, Hye Mi ; Lim, Seon Ah ; Kim, Eun Ok ; Kim, Kwanghee ; Song, Kwang Hoon ; Kim, Jiyoung ; Kumar, Vinay ; Yee, Cassian ; Doh, Junsang ; Lee, Kyung-Mi. / Homotypic NK cell-to-cell communication controls cytokine responsiveness of innate immune NK cells. In: Scientific Reports. 2014 ; Vol. 4.
@article{d5a05cd566ba410cbf6a17b46cebc55e,
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.",
author = "Kim, {Tae Jin} and Miju Kim and Kim, {Hye Mi} and Lim, {Seon Ah} and Kim, {Eun Ok} and Kwanghee Kim and Song, {Kwang Hoon} and Jiyoung Kim and Vinay Kumar and Cassian Yee and Junsang Doh and Kyung-Mi Lee",
year = "2014",
doi = "10.1038/srep07157",
language = "English",
volume = "4",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Homotypic NK cell-to-cell communication controls cytokine responsiveness of innate immune NK cells

AU - Kim, Tae Jin

AU - Kim, Miju

AU - Kim, Hye Mi

AU - Lim, Seon Ah

AU - Kim, Eun Ok

AU - Kim, Kwanghee

AU - Song, Kwang Hoon

AU - Kim, Jiyoung

AU - Kumar, Vinay

AU - Yee, Cassian

AU - Doh, Junsang

AU - Lee, Kyung-Mi

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84923348290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923348290&partnerID=8YFLogxK

U2 - 10.1038/srep07157

DO - 10.1038/srep07157

M3 - Article

VL - 4

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 7157

ER -