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Type-2 Cytokines Promote the Secretion of the Eosinophil–Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients
Several inflammatory processes of the bowel are characterized by an accumulation of eosinophils at inflammation sites. The mechanisms that govern mucosal infiltration with eosinophils are not fully understood. In this work, we studied the colorectal polyp-confined tissue containing eosinophils and w...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254714/ https://www.ncbi.nlm.nih.gov/pubmed/35799778 http://dx.doi.org/10.3389/fimmu.2022.909896 |
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author | Vaccaro, Julián Canziani, Karina Eva Guzmán, Luciana Bernedo, Viviana García, Marcela Altamirano, Eugenia Margarita Feregotti, Emanuel Curciarello, Renata Muglia, Cecilia Isabel Docena, Guillermo Horacio |
author_facet | Vaccaro, Julián Canziani, Karina Eva Guzmán, Luciana Bernedo, Viviana García, Marcela Altamirano, Eugenia Margarita Feregotti, Emanuel Curciarello, Renata Muglia, Cecilia Isabel Docena, Guillermo Horacio |
author_sort | Vaccaro, Julián |
collection | PubMed |
description | Several inflammatory processes of the bowel are characterized by an accumulation of eosinophils at inflammation sites. The mechanisms that govern mucosal infiltration with eosinophils are not fully understood. In this work, we studied the colorectal polyp-confined tissue containing eosinophils and we hypothesized that intestinal epithelial cells are the cell source of eotaxin-3 or CCL26, a potent chemoattractant for eosinophils. We analyzed colorectal polyps (n=50) from pediatric patients with rectal bleeding by H&E staining and eosin staining, and different pro-inflammatory cytokines were assessed by RT-qPCR and ELISA. IgE and CCL26 were investigated by RT-qPCR, ELISA and confocal microscopy. Finally, the intracellular signaling pathway that mediates the CCL26 production was analyzed using a kinase array and immunoblotting in human intestinal Caco-2 cell line. We found a dense cell agglomeration within the polyps, with a significantly higher frequency of eosinophils than in control adjacent tissue. IL-4 and IL-13 were significantly up-regulated in polyps and CCL26 was elevated in the epithelial compartment. Experiments with Caco-2 cells showed that the type-2 cytokine IL-13 increased STAT3 and STAT6 phosphorylation and eotaxin-3 secretion. The addition of the blocking antibody Dupilumab or the inhibitor Ruxolitinib to the cytokine-stimulated Caco-2 cells diminished the CCL26 secretion to basal levels in a dose-dependent manner. In conclusion, our findings demonstrate a high frequency of eosinophils, and elevated levels of type-2 cytokines and eotaxin-3 in the inflammatory stroma of colorectal polyps from pediatric patients. Polyp epithelial cells showed to be the main cell source of CCL26, and IL-13 was the main trigger of this chemokine through the activation of the STAT3/STAT6/JAK1-2 pathway. We suggest that the epithelial compartment actively participates in the recruitment of eosinophils to the colonic polyp-confined inflammatory environment. |
format | Online Article Text |
id | pubmed-9254714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92547142022-07-06 Type-2 Cytokines Promote the Secretion of the Eosinophil–Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients Vaccaro, Julián Canziani, Karina Eva Guzmán, Luciana Bernedo, Viviana García, Marcela Altamirano, Eugenia Margarita Feregotti, Emanuel Curciarello, Renata Muglia, Cecilia Isabel Docena, Guillermo Horacio Front Immunol Immunology Several inflammatory processes of the bowel are characterized by an accumulation of eosinophils at inflammation sites. The mechanisms that govern mucosal infiltration with eosinophils are not fully understood. In this work, we studied the colorectal polyp-confined tissue containing eosinophils and we hypothesized that intestinal epithelial cells are the cell source of eotaxin-3 or CCL26, a potent chemoattractant for eosinophils. We analyzed colorectal polyps (n=50) from pediatric patients with rectal bleeding by H&E staining and eosin staining, and different pro-inflammatory cytokines were assessed by RT-qPCR and ELISA. IgE and CCL26 were investigated by RT-qPCR, ELISA and confocal microscopy. Finally, the intracellular signaling pathway that mediates the CCL26 production was analyzed using a kinase array and immunoblotting in human intestinal Caco-2 cell line. We found a dense cell agglomeration within the polyps, with a significantly higher frequency of eosinophils than in control adjacent tissue. IL-4 and IL-13 were significantly up-regulated in polyps and CCL26 was elevated in the epithelial compartment. Experiments with Caco-2 cells showed that the type-2 cytokine IL-13 increased STAT3 and STAT6 phosphorylation and eotaxin-3 secretion. The addition of the blocking antibody Dupilumab or the inhibitor Ruxolitinib to the cytokine-stimulated Caco-2 cells diminished the CCL26 secretion to basal levels in a dose-dependent manner. In conclusion, our findings demonstrate a high frequency of eosinophils, and elevated levels of type-2 cytokines and eotaxin-3 in the inflammatory stroma of colorectal polyps from pediatric patients. Polyp epithelial cells showed to be the main cell source of CCL26, and IL-13 was the main trigger of this chemokine through the activation of the STAT3/STAT6/JAK1-2 pathway. We suggest that the epithelial compartment actively participates in the recruitment of eosinophils to the colonic polyp-confined inflammatory environment. Frontiers Media S.A. 2022-06-21 /pmc/articles/PMC9254714/ /pubmed/35799778 http://dx.doi.org/10.3389/fimmu.2022.909896 Text en Copyright © 2022 Vaccaro, Canziani, Guzmán, Bernedo, García, Altamirano, Feregotti, Curciarello, Muglia and Docena https://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 Vaccaro, Julián Canziani, Karina Eva Guzmán, Luciana Bernedo, Viviana García, Marcela Altamirano, Eugenia Margarita Feregotti, Emanuel Curciarello, Renata Muglia, Cecilia Isabel Docena, Guillermo Horacio Type-2 Cytokines Promote the Secretion of the Eosinophil–Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients |
title | Type-2 Cytokines Promote the Secretion of the Eosinophil–Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients |
title_full | Type-2 Cytokines Promote the Secretion of the Eosinophil–Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients |
title_fullStr | Type-2 Cytokines Promote the Secretion of the Eosinophil–Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients |
title_full_unstemmed | Type-2 Cytokines Promote the Secretion of the Eosinophil–Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients |
title_short | Type-2 Cytokines Promote the Secretion of the Eosinophil–Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients |
title_sort | type-2 cytokines promote the secretion of the eosinophil–attractant ccl26 by intestinal epithelial cells in food-sensitized patients |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254714/ https://www.ncbi.nlm.nih.gov/pubmed/35799778 http://dx.doi.org/10.3389/fimmu.2022.909896 |
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