IL-33 promotes innate IFN-γ production and modulates dendritic cell response in LCMV-induced hepatitis in mice

Abstract

Recent studies have revealed IL-33 as a key factor in promoting antiviral T-cell responses. However, it is less clear as to how IL-33 regulates innate immunity. In this study, we infected wild-type (WT) and IL-33 ^−/− mice with lymphocytic choriomeningitis virus (LCMV) and demonstrated an essential role of infection-induced IL-33 expression for robust innate IFN-γ production in the liver. We first shown that IL-33 deficiency resulted in a marked reduction in the number of IFN-γ ⁺ γδ T and NK cells, but an increase in that of IL-17 ⁺ γδ T cells at 16 hours post-infection. Recombinant IL-33 (rIL-33) treatment could reverse such deficiency via increasing IFN-γ-producing γδ T and NK cells, and inhibiting IL-17 ⁺ γδ T cells. We also found that rIL-33-induced type 2 innate lymphoid cells (ILC2) were not involved in T-cell responses and liver injury, since the adoptive transfer of ILC2s neither affected the IFN-γ and TNF-α production in T cells, nor liver transferase levels in LCMV-infected mice. Interestingly, we found that while IL-33 was not required for costimulatory molecule expression, it was critical for DC proliferation and cytokine production. Together, this study highlights an essential role of IL-33 in regulating innate IFN-γ-production and DC function during viral hepatitis.