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

Tae Jin Kim, Gayoung Park, Jeongmin Kim, Seon Ah Lim, Jiyoung Kim, Kyungtaek Im, Min Hwa Shin, Yang Xin Fu, Maria Luisa Del Rio, Jose Ignacio Rodriguez-Barbosa, Cassian Yee, Kyung Suk Suh, Seong Jin Kim, Sang Jun Ha, Kyung Mi Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Article number3258
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

Fingerprint

Natural Killer T-Cells
T-cells
regulators
mice
Liver
Wounds and Injuries
cells
activation
Chemical activation
bone marrow
Galactosylceramides
viruses
antigens
Virus Internalization
liver
Antigen Receptors
entry
serums
Concanavalin A
Viruses

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Kim, T. J., Park, G., Kim, J., Lim, S. A., Kim, J., Im, K., ... Lee, K. M. (2019). CD160 serves as a negative regulator of NKT cells in acute hepatic injury. Nature communications, 10(1), [3258]. https://doi.org/10.1038/s41467-019-10320-y
Kim, Tae Jin ; Park, Gayoung ; Kim, Jeongmin ; Lim, Seon Ah ; Kim, Jiyoung ; Im, Kyungtaek ; Shin, Min Hwa ; Fu, Yang Xin ; Del Rio, Maria Luisa ; Rodriguez-Barbosa, Jose Ignacio ; Yee, Cassian ; Suh, Kyung Suk ; Kim, Seong Jin ; Ha, Sang Jun ; Lee, Kyung Mi. / CD160 serves as a negative regulator of NKT cells in acute hepatic injury. In: Nature communications. 2019 ; Vol. 10, No. 1.
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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.",
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Kim, TJ, Park, G, Kim, J, Lim, SA, Kim, J, Im, K, Shin, MH, Fu, YX, Del Rio, ML, Rodriguez-Barbosa, JI, Yee, C, Suh, KS, Kim, SJ, Ha, SJ & Lee, KM 2019, 'CD160 serves as a negative regulator of NKT cells in acute hepatic injury', Nature communications, vol. 10, no. 1, 3258. https://doi.org/10.1038/s41467-019-10320-y

CD160 serves as a negative regulator of NKT cells in acute hepatic injury. / Kim, Tae Jin; Park, Gayoung; Kim, Jeongmin; Lim, Seon Ah; Kim, Jiyoung; Im, Kyungtaek; Shin, Min Hwa; Fu, Yang Xin; Del Rio, Maria Luisa; Rodriguez-Barbosa, Jose Ignacio; Yee, Cassian; Suh, Kyung Suk; Kim, Seong Jin; Ha, Sang Jun; Lee, Kyung Mi.

In: Nature communications, Vol. 10, No. 1, 3258, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Kim, Tae Jin

AU - Park, Gayoung

AU - Kim, Jeongmin

AU - Lim, Seon Ah

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AU - Im, Kyungtaek

AU - Shin, Min Hwa

AU - Fu, Yang Xin

AU - Del Rio, Maria Luisa

AU - Rodriguez-Barbosa, Jose Ignacio

AU - Yee, Cassian

AU - Suh, Kyung Suk

AU - Kim, Seong Jin

AU - Ha, Sang Jun

AU - Lee, Kyung Mi

PY - 2019/12/1

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N2 - 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.

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