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

Nature communications 2019 Jul 22

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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.

Citation

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. CD160 serves as a negative regulator of NKT cells in acute hepatic injury. Nature communications. 2019 Jul 22;10(1):3258