IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease

Initially described as Th2 promoter cytokine, more recently, IL-33 has been recognized as an alarmin, mainly in epithelial and endothelial cells. While localized in the nucleus acting as a gene regulator, it can be also released after injury, stress or inflammatory cell death. As proinflammatory sig...

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Detalles Bibliográficos
Autores principales: Pérez, Federico, Ruera, Carolina Naymé, Miculán, Emanuel Gonzalo, Carasi, Paula, Dubois Camacho, Karen, Garbi, Laura, Guzman, Luciana, Hermoso, Marcela A., Chirdo, Fernando Gabriel
Formato: Articulo
Lenguaje:Inglés
Publicado: 2020
Materias:
Biología
IL-33
ST2
Celiac disease
Alarmins
Inflammatio
Innate immunity
Small intestine
Gut immunity
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/119724
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-119724
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
IL-33
ST2
Celiac disease
Alarmins
Inflammatio
Innate immunity
Small intestine
Gut immunity
spellingShingle Biología
IL-33
ST2
Celiac disease
Alarmins
Inflammatio
Innate immunity
Small intestine
Gut immunity
Pérez, Federico
Ruera, Carolina Naymé
Miculán, Emanuel Gonzalo
Carasi, Paula
Dubois Camacho, Karen
Garbi, Laura
Guzman, Luciana
Hermoso, Marcela A.
Chirdo, Fernando Gabriel
IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease
topic_facet Biología
IL-33
ST2
Celiac disease
Alarmins
Inflammatio
Innate immunity
Small intestine
Gut immunity
description Initially described as Th2 promoter cytokine, more recently, IL-33 has been recognized as an alarmin, mainly in epithelial and endothelial cells. While localized in the nucleus acting as a gene regulator, it can be also released after injury, stress or inflammatory cell death. As proinflammatory signal, IL-33 binds to the surface receptor ST2, which enhances mast cell, Th2, regulatory T cell, and innate lymphoid cell type 2 functions. Besides these Th2 roles, free IL-33 can activate CD8+ T cells during ongoing Th1 immune responses to potentiate its cytotoxic function. Celiac Disease (CD) is a chronic inflammatory disorder characterized by a predominant Th1 response leading to multiple pathways of mucosal damage in the proximal small intestine. By immunofluorescence and western blot analysis of duodenal tissues, we found an increased expression of IL-33 in duodenal mucosa of active CD (ACD) patients. Particularly, locally digested IL-33 releases active 18/21kDa fragments which can contribute to expand the proinflammatory signal. Endothelial (CD31+) and mesenchymal, myofibroblast and pericyte cells from microvascular structures in villi and crypts, showed IL-33 nuclear location; while B cells (CD20+) showed a strong cytoplasmic staining. Both ST2 forms, ST2L and sST2, were also upregulated in duodenal mucosa of CD patients. This was accompanied by increased number of CD8+ST2+ T cells and the expression of T-bet in some ST2+ intraepithelial lymphocytes and lamina propria cells. IL-33 and sST2 mRNA levels correlated with IRF1, an IFN induced factor relevant in responses to viral infections and interferon mediated proinflammatory responses highly represented in duodenal tissues in ACD. These findings highlight the potential contribution of IL-33 and its fragments to exacerbate the proinflammatory circuit and potentiate the cytotoxic activity of CD8+ T cells in CD pathology.
format Articulo
Articulo
author Pérez, Federico
Ruera, Carolina Naymé
Miculán, Emanuel Gonzalo
Carasi, Paula
Dubois Camacho, Karen
Garbi, Laura
Guzman, Luciana
Hermoso, Marcela A.
Chirdo, Fernando Gabriel
author_facet Pérez, Federico
Ruera, Carolina Naymé
Miculán, Emanuel Gonzalo
Carasi, Paula
Dubois Camacho, Karen
Garbi, Laura
Guzman, Luciana
Hermoso, Marcela A.
Chirdo, Fernando Gabriel
author_sort Pérez, Federico
title IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease
title_short IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease
title_full IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease
title_fullStr IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease
title_full_unstemmed IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease
title_sort il-33 alarmin and its active proinflammatory fragments are released in small intestine in celiac disease
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/119724
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