title: Mouse and human Notch-1 regulate mucosal immune responses.
abstract: The Notch-1 signaling pathway is responsible for homeostatic tight junction expression in vitro, and promotes barrier function in vivo in the RAG1-adoptive transfer model of colitis. In this study, we sought to determine the role of colonic Notch-1 in the lymphoepithelial crosstalk in health and disease. We utilized in vivo and in vitro knockdown to target the expression of Notch-1. We identified that epithelial Notch-1 is required for appropriate activation of intestinal epithelial cells at steady state and upon inflammatory stimulus. Notch-1 expression modulates mucosal chemokine and cytokine secretion, and FoxP3 and effector T-cell responses. We showed that epithelial Notch-1 controls the immune function of the epithelium through crosstalk with the nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathways that, in turn, elicits T-cell responses. Overall, epithelial Notch-1 bridges innate and adaptive immunity in the gut. Our findings highlight an indispensable role for Notch-1-mediated signaling in the intricate epithelial-immune crosstalk, and validate that epithelial Notch-1 is necessary and sufficient to support protective epithelial proinflammatory responses.
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Mathern
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Laitman
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Hovhannisyan
authors.affiliation: Division of Pediatric Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: D
authors.initials: D
authors.lastname: Dunkin
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Farsio
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Malik
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: G
authors.initials: G
authors.lastname: Roda
authors.affiliation: 1] Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Division of Experimental Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA.
authors.forename: A
authors.initials: A
authors.lastname: Chitre
authors.affiliation: 1] Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Iuga
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: G
authors.initials: G
authors.lastname: Yeretssian
authors.affiliation: Division of Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Berin
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dahan
mesh_terms: D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000235:genetics; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D018928:Immunity, Mucosal / Q000502:physiology*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051881:Receptor, Notch1 / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D051881:Receptor, Notch1; D062725:Tight Junction Proteins