TY - JOUR
T1 - Aryl hydrocarbon receptor plays protective roles in cona-induced hepatic injury by both suppressing IFN-γ expression and inducing IL-22
AU - Abe, Hiromi
AU - Kimura, Akihiro
AU - Tsuruta, Sanae
AU - Fukaya, Tomohiro
AU - Sakaguchi, Ryota
AU - Morita, Rimpei
AU - Sekiya, Takashi
AU - Shichita, Takashi
AU - Chayama, Kazuaki
AU - Fujii-Kuriyama, Yoshiaki
AU - Yoshimura, Akihiko
N1 - Funding Information:
Ministry of Education, Culture, Sports, Science and Technology of Japan; the SENSIN Medical Research Foundation, the Mochida Memorial Foundation; the Uehara Memorial Foundation; KANAE foundation for the Promotion of Medical Science,; Astellas Foundation for Research on Metabolic Disorders The Ichiro Kanehara Foundation; the Takeda Science Foundation.
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
KW - AhR
KW - Hepatitis
KW - IFN-γ
KW - IL-22
KW - Innate lymphoid cells
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U2 - 10.1093/intimm/dxt049
DO - 10.1093/intimm/dxt049
M3 - Article
C2 - 24150244
AN - SCOPUS:84895831861
SN - 0953-8178
VL - 26
SP - 129
EP - 137
JO - International Immunology
JF - International Immunology
IS - 3
M1 - dxt049
ER -
