title: Aryl hydrocarbon receptor plays protective roles in ConA-induced hepatic injury by both suppressing IFN-γ expression and inducing IL-22.
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.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kimura
authors.forename: Sanae
authors.initials: S
authors.lastname: Tsuruta
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fukaya
authors.forename: Ryota
authors.initials: R
authors.lastname: Sakaguchi
authors.forename: Rimpei
authors.initials: R
authors.lastname: Morita
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Shichita
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism*; D003208:Concanavalin A / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D018183:Transplantation Chimera; D000097043:Interleukin-22
chemical_list: D003208:Concanavalin A; D004268:DNA-Binding Proteins; D007371:Interferon-gamma; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon; D000097043:Interleukin-22; C499308:Rag2 protein, mouse
keywords: AhR; IFN-γ; IL-22; hepatitis; innate lymphoid cells