IL-22-Producing RORγt-Dependent Innate Lymphoid Cells Play a Novel Protective Role in Murine Acute Hepatitis

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Abstract

Retinoid-related orphan receptor (ROR) γt is known to be related to the development and function of various immunological compartments in the liver, such as Th17 cells, natural killer T (NKT) cells, and innate lymphoid cells (ILCs). We evaluated the roles of RORγt-expressing cells in mouse acute hepatitis model using RORγt deficient (RORγt -/- ) mice and RAG-2 and RORγt double deficient (RAG-2 -/- × RORγt -/- ) mice. Acute hepatitis was induced in mice by injection with carbon tetrachloride (CCl 4 ), to investigate the regulation of liver inflammation by RORγt-expressing cells. We detected RORC expression in three compartments, CD4 + T cells, NKT cells, and lineage marker-negative SCA-1 + Thy1 high ILCs, of the liver of wild type (WT) mice. CCl 4 -treated RORγt -/- mice developed liver damage in spite of lack of RORγt-dependent cells, but with reduced infiltration of macrophages compared with WT mice. In this regard, ILCs were significantly decreased in RAG-2 -/- × RORγt -/- mice that lacked T and NKT cells. Surprisingly, RAG-2 -/- × RORγt -/- mice developed significantly severer CCl 4 -induced hepatitis compared with RAG-2 -/- mice, in accordance with the fact that hepatic ILCs failed to produce IL-22. Lastly, anti-Thy1 monoclonal antibody (mAb), but not anti-NK1.1 mAb or anti-asialo GM1 Ab administration exacerbated liver damage in RAG-2 -/- mice with the depletion of liver ILCs. Collectively, hepatic RORγt-dependent ILCs play a part of protective roles in hepatic immune response in mice. © 2013 Matsumoto et al.

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Matsumoto, A., Kanai, T., Mikami, Y., Chu, P. S., Nakamoto, N., Ebinuma, H., … Hibi, T. (2013). IL-22-Producing RORγt-Dependent Innate Lymphoid Cells Play a Novel Protective Role in Murine Acute Hepatitis. PLoS ONE, 8(4). https://doi.org/10.1371/journal.pone.0062853

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