Mouse and human Notch-1 regulate mucosal immune responses
| Autor: | Giulia Roda, David Dunkin, S Farsio, Lauren E. Laitman, Zaruhi Hovhannisyan, Stephanie Dahan, Douglas R. Mathern, M C Berin, Avantika Chitre, T J Malik, Alina Iuga, Garabet Yeretssian |
|---|---|
| Přispěvatelé: | Mathern, Dr, Laitman, Le, Hovhannisyan, Z, Dunkin, D, Farsio, S, Malik, Tj, Roda, G, Chitre, A, Iuga, Ac, Yeretssian, G, Berin, Mc, Dahan, S |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Chemokine
Colon Immunology Severity of Illness Index Cell Line Proinflammatory cytokine Mice T-Lymphocyte Subsets notch t cell Animals Humans Immunology and Allergy Receptor Notch1 Immunity Mucosal Notch 1 Mucous Membrane Tight Junction Proteins biology FOXP3 Colitis Acquired immune system Cell biology Disease Models Animal Crosstalk (biology) Gene Expression Regulation Gene Knockdown Techniques biology.protein Cytokines Cytokine secretion Chemokines Inflammation Mediators Signal transduction Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|