title: IL-33 induces nuocytes and modulates liver injury in viral hepatitis.
abstract: Molecules containing damage-associated molecular patterns play an important role in many pathogenic processes. In this study, our aim was to investigate the role of IL-33, a damage-associated molecular pattern molecule, in adenovirus (Ad)-induced liver inflammation. Ad-infected mice exhibited a steadily increased IL-33 and its receptor IL-1R-like 1 expression in the liver during the first week of infection. Treatment of exogenous IL-33 resulted in a great decrease in the serum alanine aminotransferase levels and the number of Councilman bodies in the liver. Attenuated liver injury by IL-33 correlated with an increase in T regulatory cells but with a decrease in macrophages, dendritic cells, and NK cells in the liver. IL-33 enhanced both type 1 (IL-2 and IFN-γ) and type 2 (IL-5 and IL-13) immune responses in infected mice. However, IL-33 inhibited TNF-α expression in hepatic T cells and macrophages, and significantly reduced TNF-α levels in the liver. We found that in addition to its direct effects, IL-33 strongly induced novel nuocytes in the livers and spleens of infected mice. When cocultured with nuocytes, hepatic T cells and macrophages expressed lower levels of TNF-α. The IL-33-treated mice also demonstrated a slight delay, but no significant impairment, in eliminating an intrahepatic infection with Ad. In conclusion, this study reveals that IL-33 acts as a potent immune stimulator and a hepatoprotective cytokine in acute viral hepatitis. Its direct immunoregulatory functions and ability to induce novel nuocytes further suggest to us that it may be a potentially promising therapeutic candidate for the management of viral hepatitis.
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors: Yuejin
authors: Y
authors: Liang
authors: Zuliang
authors: Z
authors: Jie
authors: Lifei
authors: L
authors: Hou
authors: Renan
authors: R
authors: Aguilar-Valenzuela
authors: David
authors: D
authors: Vu
authors: Lynn
authors: L
authors: Soong
authors: Jiaren
authors: J
authors: Sun
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006524:Hepatitis, Viral, Animal / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
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