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Intestinal non-canonical NFκB signaling shapes the local and systemic immune response.
Ramakrishnan, Sadeesh K; Zhang, Huabing; Ma, Xiaoya; Jung, Inkyung; Schwartz, Andrew J; Triner, Daniel; Devenport, Samantha N; Das, Nupur K; Xue, Xiang; Zeng, Melody Y; Hu, Yinling; Mortensen, Richard M; Greenson, Joel K; Cascalho, Marilia; Wobus, Christiane E; Colacino, Justin A; Nunez, Gabriel; Rui, Liangyou; Shah, Yatrik M.
Afiliación
  • Ramakrishnan SK; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA. ramaks@pitt.edu.
  • Zhang H; Department of Molecular & Integrative Physiology, University of Michigan, Michigan, MI, 48109, USA.
  • Ma X; Department of Molecular & Integrative Physiology, University of Michigan, Michigan, MI, 48109, USA.
  • Jung I; Department of Molecular & Integrative Physiology, University of Michigan, Michigan, MI, 48109, USA.
  • Schwartz AJ; Department of Molecular & Integrative Physiology, University of Michigan, Michigan, MI, 48109, USA.
  • Triner D; Department of Molecular & Integrative Physiology, University of Michigan, Michigan, MI, 48109, USA.
  • Devenport SN; Department of Molecular & Integrative Physiology, University of Michigan, Michigan, MI, 48109, USA.
  • Das NK; Department of Molecular & Integrative Physiology, University of Michigan, Michigan, MI, 48109, USA.
  • Xue X; Department of Molecular & Integrative Physiology, University of Michigan, Michigan, MI, 48109, USA.
  • Zeng MY; Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Hu Y; Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Mortensen RM; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA.
  • Greenson JK; Department of Molecular & Integrative Physiology, University of Michigan, Michigan, MI, 48109, USA.
  • Cascalho M; Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Wobus CE; Transplantation Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Colacino JA; Department of Surgery, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Nunez G; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Rui L; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Shah YM; Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.
Nat Commun ; 10(1): 660, 2019 02 08.
Article en En | MEDLINE | ID: mdl-30737385
Microfold cells (M-cells) are specialized cells of the intestine that sample luminal microbiota and dietary antigens to educate the immune cells of the intestinal lymphoid follicles. The function of M-cells in systemic inflammatory responses are still unclear. Here we show that epithelial non-canonical NFkB signaling mediated by NFkB-inducing kinase (NIK) is highly active in intestinal lymphoid follicles, and is required for M-cell maintenance. Intestinal NIK signaling modulates M-cell differentiation and elicits both local and systemic IL-17A and IgA production. Importantly, intestinal NIK signaling is active in mouse models of colitis and patients with inflammatory bowel diseases; meanwhile, constitutive NIK signaling increases the susceptibility to inflammatory injury by inducing ectopic M-cell differentiation and a chronic increase of IL-17A. Our work thus defines an important function of non-canonical NFkB and M-cells in immune homeostasis, inflammation and polymicrobial sepsis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 3_ND Problema de salud: 3_zoonosis Asunto principal: FN-kappa B Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 3_ND Problema de salud: 3_zoonosis Asunto principal: FN-kappa B Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos