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CD160 serves as a negative regulator of NKT cells in acute hepatic injury

Author

Listed:
  • Tae-Jin Kim

    (Korea University College of Medicine)

  • Gayoung Park

    (Korea University College of Medicine
    The University of Chicago)

  • Jeongmin Kim

    (Korea University College of Medicine)

  • Seon Ah Lim

    (Korea University College of Medicine)

  • Jiyoung Kim

    (Korea University College of Medicine)

  • Kyungtaek Im

    (Korea University College of Medicine)

  • Min Hwa Shin

    (Korea University College of Medicine)

  • Yang-Xin Fu

    (University of Texas Southwestern Medical Center)

  • Maria-Luisa Rio

    (University of Leon)

  • Jose-Ignacio Rodriguez-Barbosa

    (University of Leon)

  • Cassian Yee

    (UT MD Anderson Cancer Center)

  • Kyung-Suk Suh

    (Seoul National University College of Medicine)

  • Seong-Jin Kim

    (Precision Medicine Research Center, Advanced Institutes of Convergence Technology, Seoul National University)

  • Sang-Jun Ha

    (Yonsei University)

  • Kyung-Mi Lee

    (Korea University College of Medicine
    UT MD Anderson Cancer Center
    Northwestern University)

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.

Suggested Citation

  • Tae-Jin Kim & Gayoung Park & Jeongmin Kim & Seon Ah Lim & Jiyoung Kim & Kyungtaek Im & Min Hwa Shin & Yang-Xin Fu & Maria-Luisa Rio & Jose-Ignacio Rodriguez-Barbosa & Cassian Yee & Kyung-Suk Suh & Seo, 2019. "CD160 serves as a negative regulator of NKT cells in acute hepatic injury," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10320-y
    DOI: 10.1038/s41467-019-10320-y
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    Cited by:

    1. Guozhong Jiang & Zhizhong Wang & Zhenguo Cheng & Weiwei Wang & Shuangshuang Lu & Zifang Zhang & Chinedu A. Anene & Faraz Khan & Yue Chen & Emma Bailey & Huisha Xu & Yunshu Dong & Peinan Chen & Zhongxi, 2024. "The integrated molecular and histological analysis defines subtypes of esophageal squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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