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 journalArticlepeer-review

5 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

Bibliographical note

Funding Information:
We thank the NIH Tetramer Core Facility for providing PBS 57 ligand loaded CD1d Tetramers. Further, we thank the staffs of Gyerim Experimental Animal Resource Center for animal care and technical assistance. K.-M. Lee was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future planning (NRF-2016M3A9B6948342, NRF-2017R1A2B3004828, and NRF-2018M3A9D3079288). S.-J. Kim was supported by the Korea Health Industry Development Institute (KHIDI-HI14C2640) grant funded by Korea Government. S.-J. Ha was supported by a grant from the NRF (NRF-2018R1A2A1A05076997). T.-J. Kim was additionally supported by a grant from the NRF (NRF-2016R1A6A3A04009698).

Publisher Copyright:
© 2019, The Author(s).

All Science Journal Classification (ASJC) codes

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

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