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

Hiromi Abe, Akihiro Kimura, Sanae Tsuruta, Tomohiro Fukaya, Ryota Sakaguchi, Rimpei Morita, Takashi Sekiya, Takashi Shichita, Kazuaki Chayama, Yoshiaki Fujii-Kuriyama, Akihiko Yoshimura

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Article numberdxt049
Pages (from-to)129-137
Number of pages9
JournalInternational Immunology
Volume26
Issue number3
DOIs
Publication statusPublished - 2014

Fingerprint

Aryl Hydrocarbon Receptors
Hepatitis
Liver
Wounds and Injuries
Natural Killer T-Cells
Lymphocytes
Environmental Pollutants
Poisons
Tretinoin
Hypersensitivity
Transcription Factors
Bone Marrow
interleukin-22
Ligands

Keywords

  • AhR
  • Hepatitis
  • IFN-γ
  • IL-22
  • Innate lymphoid cells

ASJC Scopus subject areas

  • Immunology

Cite this

Aryl hydrocarbon receptor plays protective roles in cona-induced hepatic injury by both suppressing IFN-γ expression and inducing IL-22. / Abe, Hiromi; Kimura, Akihiro; Tsuruta, Sanae; Fukaya, Tomohiro; Sakaguchi, Ryota; Morita, Rimpei; Sekiya, Takashi; Shichita, Takashi; Chayama, Kazuaki; Fujii-Kuriyama, Yoshiaki; Yoshimura, Akihiko.

In: International Immunology, Vol. 26, No. 3, dxt049, 2014, p. 129-137.

Research output: Contribution to journalArticle

Abe, H, Kimura, A, Tsuruta, S, Fukaya, T, Sakaguchi, R, Morita, R, Sekiya, T, Shichita, T, Chayama, K, Fujii-Kuriyama, Y & Yoshimura, A 2014, 'Aryl hydrocarbon receptor plays protective roles in cona-induced hepatic injury by both suppressing IFN-γ expression and inducing IL-22', International Immunology, vol. 26, no. 3, dxt049, pp. 129-137. https://doi.org/10.1093/intimm/dxt049
Abe, Hiromi ; Kimura, Akihiro ; Tsuruta, Sanae ; Fukaya, Tomohiro ; Sakaguchi, Ryota ; Morita, Rimpei ; Sekiya, Takashi ; Shichita, Takashi ; Chayama, Kazuaki ; Fujii-Kuriyama, Yoshiaki ; Yoshimura, Akihiko. / Aryl hydrocarbon receptor plays protective roles in cona-induced hepatic injury by both suppressing IFN-γ expression and inducing IL-22. In: International Immunology. 2014 ; Vol. 26, No. 3. pp. 129-137.
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