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Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat
Our understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074767/ https://www.ncbi.nlm.nih.gov/pubmed/33924264 http://dx.doi.org/10.3390/ijms22084292 |
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author | Madeira, Ana Serena, Carolina Ejarque, Miriam Maymó-Masip, Elsa Millan, Monica Navarro-Ruiz, M. Carmen Guzmán-Ruiz, Rocío Malagón, María M. Espin, Eloy Martí, Marc Menacho, Margarita Megía, Ana Vendrell, Joan Fernández-Veledo, Sonia |
author_facet | Madeira, Ana Serena, Carolina Ejarque, Miriam Maymó-Masip, Elsa Millan, Monica Navarro-Ruiz, M. Carmen Guzmán-Ruiz, Rocío Malagón, María M. Espin, Eloy Martí, Marc Menacho, Margarita Megía, Ana Vendrell, Joan Fernández-Veledo, Sonia |
author_sort | Madeira, Ana |
collection | PubMed |
description | Our understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and their progenitors, we explored whether the dysfunctional obese and Crohn’s disease environments influence the mesothelial/mesenchymal properties of their adipocyte precursors, as well as their ability to mount an immune response. Using a tandem transcriptomic/proteomic approach, we evaluated the mesothelial and mesenchymal expression profiles in adipose tissue, both in subjects covering a wide range of body-mass indexes and in Crohn’s disease patients. We also isolated adipose tissue precursors (adipose-derived stem cells, ASCs) to assess their mesothelial/mesenchymal properties, as well as their antigen-presenting features. Human visceral tissue presented a mesothelial phenotype not detected in the subcutaneous fat. Only ASCs from mesenteric adipose tissue, named creeping fat, had a significantly higher expression of the hallmark mesothelial genes mesothelin (MSLN) and Wilms’ tumor suppressor gene 1 (WT1), supporting a mesothelial nature of these cells. Both lean and Crohn’s disease visceral ASCs expressed equivalent surface percentages of the antigen-presenting molecules human leucocyte antigen—DR isotype (HLA-DR) and CD86. However, lean-derived ASCs were predominantly HLA-DR (dim), whereas in Crohn’s disease, the HLA-DR (bright) subpopulation was increased 3.2-fold. Importantly, the mesothelial-enriched Crohn’s disease precursors activated CD4(+) T-lymphocytes. Our study evidences a mesothelial signature in the creeping fat of Crohn’s disease patients and its progenitor cells, the latter being able to present antigens and orchestrate an immune response. |
format | Online Article Text |
id | pubmed-8074767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80747672021-04-27 Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat Madeira, Ana Serena, Carolina Ejarque, Miriam Maymó-Masip, Elsa Millan, Monica Navarro-Ruiz, M. Carmen Guzmán-Ruiz, Rocío Malagón, María M. Espin, Eloy Martí, Marc Menacho, Margarita Megía, Ana Vendrell, Joan Fernández-Veledo, Sonia Int J Mol Sci Article Our understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and their progenitors, we explored whether the dysfunctional obese and Crohn’s disease environments influence the mesothelial/mesenchymal properties of their adipocyte precursors, as well as their ability to mount an immune response. Using a tandem transcriptomic/proteomic approach, we evaluated the mesothelial and mesenchymal expression profiles in adipose tissue, both in subjects covering a wide range of body-mass indexes and in Crohn’s disease patients. We also isolated adipose tissue precursors (adipose-derived stem cells, ASCs) to assess their mesothelial/mesenchymal properties, as well as their antigen-presenting features. Human visceral tissue presented a mesothelial phenotype not detected in the subcutaneous fat. Only ASCs from mesenteric adipose tissue, named creeping fat, had a significantly higher expression of the hallmark mesothelial genes mesothelin (MSLN) and Wilms’ tumor suppressor gene 1 (WT1), supporting a mesothelial nature of these cells. Both lean and Crohn’s disease visceral ASCs expressed equivalent surface percentages of the antigen-presenting molecules human leucocyte antigen—DR isotype (HLA-DR) and CD86. However, lean-derived ASCs were predominantly HLA-DR (dim), whereas in Crohn’s disease, the HLA-DR (bright) subpopulation was increased 3.2-fold. Importantly, the mesothelial-enriched Crohn’s disease precursors activated CD4(+) T-lymphocytes. Our study evidences a mesothelial signature in the creeping fat of Crohn’s disease patients and its progenitor cells, the latter being able to present antigens and orchestrate an immune response. MDPI 2021-04-20 /pmc/articles/PMC8074767/ /pubmed/33924264 http://dx.doi.org/10.3390/ijms22084292 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Madeira, Ana Serena, Carolina Ejarque, Miriam Maymó-Masip, Elsa Millan, Monica Navarro-Ruiz, M. Carmen Guzmán-Ruiz, Rocío Malagón, María M. Espin, Eloy Martí, Marc Menacho, Margarita Megía, Ana Vendrell, Joan Fernández-Veledo, Sonia Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat |
title | Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat |
title_full | Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat |
title_fullStr | Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat |
title_full_unstemmed | Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat |
title_short | Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat |
title_sort | crohn’s disease increases the mesothelial properties of adipocyte progenitors in the creeping fat |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074767/ https://www.ncbi.nlm.nih.gov/pubmed/33924264 http://dx.doi.org/10.3390/ijms22084292 |
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