IL-33 promotes innate IFN-γ production and modulates dendritic cell response in LCMV-induced hepatitis in mice.
IL-33 promotes innate IFN-γ production and modulates dendritic cell response in LCMV-induced hepatitis in mice.
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DOI：
10.1002/eji.201545696
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发表时间：
2015-11
影响因子：
5.4
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Liang Y;Jie Z;Hou L;Yi P;Wang W;Kwota Z;Salvato M;de Waal Malefyt R;Soong L;Sun J
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.
