IL32γ activates natural killer receptor-expressing innate immune cells to produce IFNγ via dendritic cell-derived IL12

Sung Won Lee; Hyun Jung Park; Kwang Soo Lee; Se-Ho Park; Soohyun Kim; Sung Ho Jeon; Seokmann Hong

doi:10.1016/j.bbrc.2015.03.174

IL32γ activates natural killer receptor-expressing innate immune cells to produce IFNγ via dendritic cell-derived IL12

Biochem Biophys Res Commun. 2015 May 22;461(1):86-94. doi: 10.1016/j.bbrc.2015.03.174. Epub 2015 Apr 6.

Authors

Sung Won Lee¹, Hyun Jung Park², Kwang Soo Lee³, Se-Ho Park⁴, Soohyun Kim⁵, Sung Ho Jeon³, Seokmann Hong⁶

Affiliations

¹ Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul, 143-747, South Korea; School of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, South Korea.
² Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul, 143-747, South Korea.
³ Department of Life Science, Hallym University, Chuncheon, 200-702, South Korea.
⁴ School of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, South Korea.
⁵ Department of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, South Korea.
⁶ Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul, 143-747, South Korea. Electronic address: shong@sejong.ac.kr.

PMID: 25858316
DOI: 10.1016/j.bbrc.2015.03.174

Abstract

The inflammatory cytokine IL32γ acts on dendritic cells (DCs) to produce IL12 and IL6, which are involved in the differentiation of Th1 and Th17 cells. Natural killer (NK) and NKT cells play important roles in IL12-mediated adaptive immune responses, such as antitumor immunity. Herein we demonstrate the effect of IL32γ on the activation of NK and NKT cells. Upon IL32γ stimulation, splenic NK and NKT cells could be activated, and this activation was dependent on both IL12 and DCs, which was confirmed by using IL12p35 knockout and CD11c-diphtheria toxin receptor transgenic mouse models. Furthermore, IL32γ could induce the production of proinflammatory cytokines by NKDCs, a subset of DCs expressing NK cell markers, known to enhance NKT cell function. Unlike conventional DCs, NKDCs produced IFNγ and TNFα rather than IL12 upon stimulation with IL32γ. Taken together, IL32γ will be useful as an adjuvant to boost the cytotoxicities of NK and NKT cells that play critical roles in antitumor immunity.

Keywords: IFNγ; IL12; IL32γ; NK; NKDC; NKT.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Communication / immunology
Cells, Cultured
Dendritic Cells / immunology*
Immunity, Innate / immunology*
Interferon-gamma / immunology*
Interleukin-12 / immunology*
Interleukins / immunology*
Killer Cells, Natural / immunology*
Mice
Mice, Inbred C57BL
Natural Killer T-Cells / immunology*

Substances

Interleukins
interleukin-32, mouse
Interleukin-12
Interferon-gamma