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

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 ?-galactosylceramide (?-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-?, TNF, and IL-4 production. Lastly, inhibition of BTLA by anti-BTLA mAb aggravates ?-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.

SUBMITTER: Kim TJ 

PROVIDER: S-EPMC6646315 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature