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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578377/ https://www.ncbi.nlm.nih.gov/pubmed/33133101 http://dx.doi.org/10.3389/fimmu.2020.581445 |
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author | Perez, Federico Ruera, Carolina N. Miculan, Emanuel Carasi, Paula Dubois-Camacho, Karen Garbi, Laura Guzman, Luciana Hermoso, Marcela A. Chirdo, Fernando G. |
author_facet | Perez, Federico Ruera, Carolina N. Miculan, Emanuel Carasi, Paula Dubois-Camacho, Karen Garbi, Laura Guzman, Luciana Hermoso, Marcela A. Chirdo, Fernando G. |
author_sort | Perez, Federico |
collection | PubMed |
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 | Online Article Text |
id | pubmed-7578377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75783772020-10-30 IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease Perez, Federico Ruera, Carolina N. Miculan, Emanuel Carasi, Paula Dubois-Camacho, Karen Garbi, Laura Guzman, Luciana Hermoso, Marcela A. Chirdo, Fernando G. Front Immunol Immunology 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. Frontiers Media S.A. 2020-10-08 /pmc/articles/PMC7578377/ /pubmed/33133101 http://dx.doi.org/10.3389/fimmu.2020.581445 Text en Copyright © 2020 Perez, Ruera, Miculan, Carasi, Dubois-Camacho, Garbi, Guzman, Hermoso and Chirdo http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Perez, Federico Ruera, Carolina N. Miculan, Emanuel Carasi, Paula Dubois-Camacho, Karen Garbi, Laura Guzman, Luciana Hermoso, Marcela A. Chirdo, Fernando G. IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease |
title | 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_short | 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 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578377/ https://www.ncbi.nlm.nih.gov/pubmed/33133101 http://dx.doi.org/10.3389/fimmu.2020.581445 |
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