Dysregulated balance of retinoid-related orphan receptor γt-dependent innate lymphoid cells is involved in the pathogenesis of chronic DSS-induced colitis.

Abstract

Retinoid-related orphan receptor (ROR) γt-expressing and IL-22-producing NKp46(+) innate lymphoid (ILC22) cells reside in the lamina propria of the intestine in mice, suggesting that ILC22 cells contribute to host defense during intestinal damage in models of colitis in mice. Nevertheless, another set of pathological interferon (IFN)-γ and/or IL-17A-producing innate lymphoid cells (ILC1 and ICL17) may participate in the pathogenesis in different models of colitis. We here showed that RORγt(+)IL-22(+) ILC22 cells were localized in Thy-1(high)SCA-1(high) and/or Thy-1(high)SCA-1(low) subpopulations of the intestine in normal and dextran sodium sulfate (DSS)-induced colitic RORγt-sufficient Rag-2(-/-) mice. RORγt-deficient Rag-2(-/-) mice developed more severe DSS-induced colitis accompanied with lower expression of REG3β and REG3γ in the colon, but with a lower ratio and absolute number of IFN-γ-producing ILC1 cells as compared to control RORγt-sufficient Rag-2(-/-) mice. Collectively, not only the presence of ILC22 cells but also the balance of protective and pathogenic ILCs may be involved in the prevention of colitis.

• Authors: Kayoko Kimura, Takanori Kanai, Atsushi Hayashi, Yohei Mikami, Tomohisa Sujino, Shinta Mizuno, Tango Handa, Katsuyoshi Matsuoka, Tadakazu Hisamatsu, Toshiro Sato, Toshifumi Hibi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 427 Issue 4 Pg. 694-700 (Nov 02 2012) ISSN: 1090-2104 [Electronic] United States
• PMID: 23022186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• DNA-Binding Proteins
• Il17a protein, mouse
• Interleukin-17
• Interleukins
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Rag2 protein, mouse
• Dextran Sulfate

Topics

• Animals
• Cell Line
• Colitis (chemically induced, immunology, pathology)
• DNA-Binding Proteins (genetics)
• Dextran Sulfate (pharmacology)
• Disease Models, Animal
• Gene Knockdown Techniques
• Genes, Reporter
• Immunity, Innate
• Interleukin-17 (immunology)
• Interleukins (immunology)
• Intestines (immunology, pathology)
• Lymphocytes (immunology)
• Mice
• Mice, Mutant Strains
• Nuclear Receptor Subfamily 1, Group F, Member 3 (genetics, immunology)
• Interleukin-22