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IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies.
Yamazaki, Soh; Inohara, Naohiro; Ohmuraya, Masaki; Tsuneoka, Yousuke; Yagita, Hideo; Katagiri, Takaharu; Nishina, Takashi; Mikami, Tetuo; Funato, Hiromasa; Araki, Kimi; Nakano, Hiroyasu.
Afiliação
  • Yamazaki S; Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan. syamaz@med.toho-u.ac.jp.
  • Inohara N; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
  • Ohmuraya M; Department of Genetics, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
  • Tsuneoka Y; Department of Anatomy, Toho University School of Medicine, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan.
  • Yagita H; Department of Immunology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, 113-8421, Japan.
  • Katagiri T; Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan.
  • Nishina T; Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan.
  • Mikami T; Department of Pathology, Toho University School of Medicine, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan.
  • Funato H; Department of Anatomy, Toho University School of Medicine, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan.
  • Araki K; International Institutes for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
  • Nakano H; Division of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto University, 2-2-1, Honjo, Kumamoto, 860-0811, Japan.
Mucosal Immunol ; 15(6): 1321-1337, 2022 06.
Article em En | MEDLINE | ID: mdl-35999460
Control of gut microbes is crucial for not only local defense in the intestine but also proper systemic immune responses. Although intestinal epithelial cells (IECs) play important roles in cytokine-mediated control of enterobacteria, the underlying mechanisms are not fully understood. Here we show that deletion of IκBζ in IECs in mice leads to dysbiosis with marked expansion of segmented filamentous bacteria (SFB), thereby enhancing Th17 cell development and exacerbating inflammatory diseases. Mechanistically, the IκBζ deficiency results in decrease in the number of Paneth cells and impairment in expression of IL-17-inducible genes involved in IgA production. The decrease in Paneth cells is caused by aberrant activation of IFN-γ signaling and a failure of IL-17-dependent recovery from IFN-γ-induced damage. Thus, the IL-17R-IκBζ axis in IECs contributes to the maintenance of intestinal homeostasis by serving as a key component in a regulatory loop between the gut microbiota and immune cells.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-17 / Células Th17 / Disbiose Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Mucosal Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-17 / Células Th17 / Disbiose Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Mucosal Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Japão
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