IL-33 promotes innate IFN-? 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 and demonstrated an essential role of infection-induced IL-33 expression for robust innate IFN-? production in the liver. We first show that IL-33 deficiency resulted in a marked reduction in the number of IFN-?(+) ?? T and NK cells, but an increase in that of IL-17(+) ?? T cells at 16 h postinfection. Recombinant IL-33 (rIL-33) treatment could reverse such deficiency via increasing IFN-?-producing ?? T and NK cells, and inhibiting IL-17(+) ?? T cells. We also found that rIL-33-induced type 2 innate lymphoid cells were not involved in T-cell responses and liver injury, since the adoptive transfer of type 2 innate lymphoid cells neither affected the IFN-? and TNF-? production in T cells, nor liver transferase levels in lymphocytic choriomeningitis virus 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-?-production and DC function during viral hepatitis.

SUBMITTER: Liang Y 

PROVIDER: S-EPMC4813322 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature