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

Atsuhiro Matsumoto, Takanori Kanai, Yohei Mikami, Po Sung Chu, Nobuhiro Nakamoto, Hirotoshi Ebinuma, Hidetsugu Saito, Toshiro Sato, Hideo Yagita, Toshifumi Hibi

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32 Citations (Scopus)


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 (CCl4), 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+Thy1high ILCs, of the liver of wild type (WT) mice. CCl4-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 CCl4-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.

Original languageEnglish
Article numbere62853
JournalPloS one
Issue number4
Publication statusPublished - 2013 Apr 23

ASJC Scopus subject areas

  • General


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