IL-33 promotes IFN-γ production by group 1 innate lymphoid cells in viral hepatitis (IRC8P.490)

Abstract

Abstract Innate immune response is the first line of the defense against the viral pathogens. The damage associated molecular patterns (DAMP) molecule IL-33 has been proved to be critical for T cell response in viral persistent infection. However, its role in modulating the innate immune response in viral infection is not clear. Herein, we injected the mice with lymphocytic choriomeningitis virus (LCMV) Clone 13 and found that the hepatic gene expression of IL-33 was upregulated at 1 day post-infection (dpi) and reached the peak at 6 dpi. Deficiency of IL-33 not only led to impaired anti-viral T cell responses (low IFN-γ and TNF-α), but also resulted in less numbers of IFN-γ+ innate immune cells, such as NK and γδT cells at 16h postinfection. Treatment of recombinant IL-33 (rIL-33) significantly increased the percentages of IFN-γ +γδT cells. In vitro, rIL-33 inhibited proliferation of IL-17+γδ T cells, but increased IFN-γ+γδ T cells in a dose-dependent manner. rIL-33 treatment also upregulated IFN-γ and granzyme B expression in NK cells in vitro culture. More importantly, hepatic dendritic cells (DC) in IL-33 knockout mice expressed lower level of IL-12 compared with control mice, indicating that deficiency of IL-33 may impair the DC priming. Our data reveal the key role of IL-33 in promoting IFN-γ production by group 1 innate lymphoid cells and subsequently regulate the anti-viral T cell response in viral hepatitis.