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Title: Intestinal non-canonical NFκB signaling shapes the local and systemic immune response.

Authors: 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

Published In Nat Commun, (2019 Feb 08)

Abstract: 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.

PubMed ID: 30737385 Exiting the NIEHS site

MeSH Terms: Animals; B-Lymphocytes/metabolism; Blotting, Western; Colitis/immunology; Colitis/metabolism; Colon/metabolism; Colon/pathology; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Immunoglobulin A/metabolism; Interleukin-17/metabolism; Intestines/immunology; Mice; NF-kappa B/metabolism*; Protein Serine-Threonine Kinases; RNA, Ribosomal, 16S/genetics; Sepsis/genetics; Sepsis/metabolism; Signal Transduction/physiology

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