박가영 (고려대학교 의과대학, The University of Chicago)

한빛사논문

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고려대학교 의과대학, The University of Chicago

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Nat. Commun., Published 22 July 2019, 10, Article number: 3258 | DOI https://doi.org/10.1038/s41467-019-10320-y CD160 serves as a negative regulator of NKT cells in acute hepatic injury

Tae-Jin Kim^1,10, Gayoung Park^1,2,10, Jeongmin Kim¹, Seon Ah Lim¹, Jiyoung Kim¹, Kyungtaek Im¹, Min Hwa Shin¹, Yang-Xin Fu³, Maria-Luisa Del Rio⁴, Jose-Ignacio Rodriguez-Barbosa⁴, Cassian Yee⁵, Kyung-Suk Suh⁶, Seong-Jin Kim⁷, Sang-Jun Ha^8,* & Kyung-Mi Lee^1,5,9,*

¹ Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 02841, Republic of Korea.² Department of Medicine, Section of Dermatology, The University of Chicago, Chicago, IL 60637, USA. ³ Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.⁴ Transplantation Immunobiology Section, Institute of Biomedicine, University of Leon, Leon 24071, Spain. ⁵Department of Melanoma Medical Oncology and department of Immunology, UT MD Anderson Cancer Center, Houston, TX 77054, USA.⁶ Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. ⁷ Precision Medicine Research Center, Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyeonggi-do 16229, Republic of Korea.⁸ Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea. ⁹Department of Biomedical Engineering, Center for Bio-Integrated Electronics, Simpson Querrey Institute for BioNanotechnology, Northwestern University, Evanston, IL 60208, USA. ¹⁰These authors contributed equally: Tae-Jin Kim, Gayoung Park

^*Correspondence and requests for materials should be addressed to S.-J.H. or to K.-M.L.

Abstract

CD160 and BTLA both bind to herpes virus entry mediator. Although a negative regulatory function of BTLA in natural killer T (NKT) cell activation has been reported, whether CD160 is also involved is unclear. By analyzing CD160^−/− mice and mixed bone marrow chimeras, we show that CD160 is not essential for NKT cell development. However, CD160^−/− mice exhibit severe liver injury after in vivo challenge with α-galactosylceramide (α-GalCer). Moreover, CD160^−/− mice are more susceptible to Concanavalin A challenge, and display elevated serum AST and ALT levels, hyperactivation of NKT cells, and enhanced IFN-γ, TNF, and IL-4 production. Lastly, inhibition of BTLA by anti-BTLA mAb aggravates α-GalCer-induced hepatic injury in CD160^−/−mice, suggesting that both CD160 and BTLA serve as non-overlapping negative regulators of NKT cells. Our data thus implicate CD160 as a co-inhibitory receptor that delivers antigen-dependent signals in NKT cells to dampen cytokine production during early innate immune activation.

논문정보

형식Research article
게재일2019년 07월 (BRIC 등록일 2019-07-30)
연구진국내(교신)+국외 연구진
분야 생명과학 > 면역학

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