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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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