| First Author | Matsumoto A | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 4 | Pages | e62853 |
| PubMed ID | 23626860 | Mgi Jnum | J:200099 |
| Mgi Id | MGI:5506985 | Doi | 10.1371/journal.pone.0062853 |
| Citation | Matsumoto A, et al. (2013) IL-22-producing RORgammat-dependent innate lymphoid cells play a novel protective role in murine acute hepatitis. PLoS One 8(4):e62853 |
| abstractText | Retinoid-related orphan receptor (ROR) gammat 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 RORgammat-expressing cells in mouse acute hepatitis model using RORgammat deficient (RORgammat(-/-)) mice and RAG-2 and RORgammat double deficient (RAG-2(-/-) x RORgammat(-/-)) mice. Acute hepatitis was induced in mice by injection with carbon tetrachloride (CCl4), to investigate the regulation of liver inflammation by RORgammat-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. CCl4-treated RORgammat(-/-) mice developed liver damage in spite of lack of RORgammat-dependent cells, but with reduced infiltration of macrophages compared with WT mice. In this regard, ILCs were significantly decreased in RAG-2(-/-) x RORgammat(-/-) mice that lacked T and NKT cells. Surprisingly, RAG-2(-/-) x RORgammat(-/-) 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 RORgammat-dependent ILCs play a part of protective roles in hepatic immune response in mice. |
