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Int Immunol. 2014 Mar;26(3):129-37. doi: 10.1093/intimm/dxt049. Epub 2013 Oct 22.

Aryl hydrocarbon receptor plays protective roles in ConA-induced hepatic injury by both suppressing IFN-γ expression and inducing IL-22.

Author information

1
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.

Abstract

The aryl hydrocarbon receptor (AhR), a ligand-activated nuclear transcription factor, is known to mediate the toxic and carcinogenic effects of various environmental pollutants, while AhR has been shown to protect animals from various types of tissue injury. ConA-induced hepatitis is known as a mouse model of acute liver injury. Here, we found a protective role of AhR in ConA-induced hepatitis. AhR is induced in the liver during ConA-induced hepatitis, and Ahr (-/-) mice were highly sensitive to this model. Bone marrow chimera experiments indicate that Ahr (-/-) hematopoietic cells are responsible for hypersensitivity to ConA-induced hepatitis. We found that IFN-γ from invariant NKT cells was up-regulated and IL-22 from innate lymphoid cells (ILCs) was abolished in Ahr (-/-) mice. In addition, IL-22 production was still observed in Rag2 (-/-) mice but it was severely reduced in Ahr (-/-) Rag2 (-/-) mice. ConA-induced IL-22 production was also dependent on retinoic acid-related orphan receptor γt. These results show that AhR has crucial protective roles in ConA-induced liver injury via promoting IL-22 production from ILCs and suppressing IFN-γ expression from NKT cells.

KEYWORDS:

AhR; IFN-γ; IL-22; hepatitis; innate lymphoid cells

PMID:
24150244
DOI:
10.1093/intimm/dxt049
[Indexed for MEDLINE]

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