CD160 Serves As a Negative Regulator of NKT Cells in Acute Hepatic Injury

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Jul 24

PMID 31332204

Citations 18

Authors

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

Affiliations

Soon will be listed here.

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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