Overexpression of corticotropin-releasing factor in intestinal mucosal eosinophils is associated with clinical severity in Diarrhea-Predominant Irritable Bowel Syndrome

Corticotropin-releasing factor (CRF) has been identified in intestinal mucosal eosinophils and associated with psychological stress and gut dysfunction. Irritable bowel syndrome (IBS) is commonly characterized by altered intestinal motility, immune activation, and increased gut barrier permeability...

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Autores: Salvo-Romero, Eloísa, Martínez, Cristina|||0000-0002-9368-1356, Lobo Álvarez, Beatriz|||0000-0003-3391-7125, Rodiño-Janeiro, Bruno K.|||0000-0002-0633-6774, Pigrau Pastor, Marc|||0000-0001-6801-3017, Sánchez Chardi, Alejandro|||0000-0002-8789-1883, González Castro, Ana Maria|||0000-0003-3955-3318, Fortea, Marina|||0000-0001-8885-7495, Pardo-Camacho, Cristina, Nieto Ruiz, Adoración|||0000-0002-3421-2840, Expósito, Elba|||0000-0001-6088-3149, Guagnozzi, Danila|||0000-0002-6171-1901, Rodríguez-Urrutia, Amanda|||0000-0001-6882-205X, de Torres, Inés|||0000-0002-5495-9140, Farré, Ricard|||0000-0001-7158-171X, Azpiroz Vidaur, Fernando|||0000-0002-7327-960X, Alonso Cotoner, Carmen|||0000-0002-3483-2919, Santos, Javier|||0000-0002-4798-5033, Vicario Perez, Maria|||0000-0001-9622-3185
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:253129
Acceso en línea:https://ddd.uab.cat/record/253129
https://dx.doi.org/urn:doi:10.1038/s41598-020-77176-x
Access Level:acceso abierto
Palabra clave:Irritable bowel syndrome
Mucosal immunology
Descripción
Sumario:Corticotropin-releasing factor (CRF) has been identified in intestinal mucosal eosinophils and associated with psychological stress and gut dysfunction. Irritable bowel syndrome (IBS) is commonly characterized by altered intestinal motility, immune activation, and increased gut barrier permeability along with heightened susceptibility to psychosocial stress. Despite intensive research, the role of mucosal eosinophils in stress-associated gut dysfunction remains uncertain. In this study, we evaluated eosinophil activation profile and CRF content in the jejunal mucosa of diarrhea-predominant IBS (IBS-D) and healthy controls (HC) by gene/protein expression and transmission electron microscopy. We also explored the association between intestinal eosinophil CRF and chronic stress, and the potential mechanisms underlying the stress response by assessing eosinophil response to neuropeptides. We found that mucosal eosinophils displayed higher degranulation profile in IBS-D as compared to HC, with increased content of CRF in the cytoplasmic granules, which significantly correlated with IBS clinical severity, life stress background and depression. Eosinophils responded to substance P and carbachol by increasing secretory activity and CRF synthesis and release, without promoting pro-inflammatory activity, a profile similar to that found in mucosal eosinophils from IBS-D. Collectively, our results suggest that intestinal mucosal eosinophils are potential contributors to stress-mediated gut dysfunction through CRF production and release.

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