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Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn’s disease
BACKGROUND: Crohn’s disease (CD) is a multifactorial disease characterized by chronic intestinal inflammation. The increased visceral adiposity near the affected intestinal area, of which mesenteric adipose tissue (MAT) is the main component, is a feature of CD. Both protective and pathological role...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993458/ https://www.ncbi.nlm.nih.gov/pubmed/32000799 http://dx.doi.org/10.1186/s12967-020-02220-3 |
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author | da Silva, Francesca Aparecida Ramos Pascoal, Lívia Bitencourt Dotti, Isabella Setsuko Ayrizono, Maria de Lourdes Aguilar, Daniel Rodrigues, Bruno Lima Arroyes, Montserrat Ferrer-Picon, Elena Milanski, Marciane Velloso, Lício Augusto Fagundes, João José Salas, Azucena Leal, Raquel Franco |
author_facet | da Silva, Francesca Aparecida Ramos Pascoal, Lívia Bitencourt Dotti, Isabella Setsuko Ayrizono, Maria de Lourdes Aguilar, Daniel Rodrigues, Bruno Lima Arroyes, Montserrat Ferrer-Picon, Elena Milanski, Marciane Velloso, Lício Augusto Fagundes, João José Salas, Azucena Leal, Raquel Franco |
author_sort | da Silva, Francesca Aparecida Ramos |
collection | PubMed |
description | BACKGROUND: Crohn’s disease (CD) is a multifactorial disease characterized by chronic intestinal inflammation. The increased visceral adiposity near the affected intestinal area, of which mesenteric adipose tissue (MAT) is the main component, is a feature of CD. Both protective and pathological roles have been attributed to this disease-associated tissue in CD. To understand the contribution of MAT to CD pathophysiology, a molecular and cellular signature of disease-associated MAT in CD patients was provided. METHODS: We performed an observational study with whole transcriptional analysis by RNA sequencing (RNA-seq) of MAT and ileal mucosa from CD patients with active disease and controls. qPCR and immunohistology were performed for validation analysis. RESULTS: RNA-seq identified 17 significantly regulated genes (|FC| > 1.5; FDR < 0.05) in CD-MAT compared to non-IBD controls, with a marked upregulation of plasma cell genes (i.e., IGLL5, MZB1, CD79A, POU2AF1, FCRL5, JCHAIN, DERL3, SDC1, PIM2). A less strict statistical cutoff value (|FC| > 1.5, nominal p ≤ 0.05) yielded a larger list of 651 genes in CD-MAT compared to controls. CD ileum showed the significant regulation compared to control ileum of 849 genes (|FC| > 1.5; FDR < 0.05) or 2654 genes (|FC| > 1.5, nominal p ≤ 0.05). Ingenuity Pathway Analysis revealed the significant regulation of pathways related to T- and B cell functionality in the MAT of CD patients. Despite the differences between the MAT and ileal signatures of CD patients, we identified a subset of 204 genes significantly modulated in both tissues compared to controls. This common signature included genes related to the plasma cell signature. Genes such as S100A8, S100A9 (calprotectin) and IL1B, which are associated with acute inflammatory response, were exclusively regulated in the ileal mucosa of CD disease. In contrast, some genes encoding for lymphocyte receptors such as MS4A1, CD3D and CD79A were exclusively regulated in CD-MAT, exhibiting a different pattern of immune cell activation compared to the ileal mucosa in CD patients. qPCR and immunohistology confirmed the presence of large infiltrates of CD3(+) CD20(+) lymphocytes and CD138(+) plasma cells in CD-MAT. CONCLUSION: Our data strongly supports the role of CD-associated MAT as a site for T-, B- and plasma cell activation, and suggests that it could also act as a reservoir of memory immune responses. |
format | Online Article Text |
id | pubmed-6993458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69934582020-02-04 Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn’s disease da Silva, Francesca Aparecida Ramos Pascoal, Lívia Bitencourt Dotti, Isabella Setsuko Ayrizono, Maria de Lourdes Aguilar, Daniel Rodrigues, Bruno Lima Arroyes, Montserrat Ferrer-Picon, Elena Milanski, Marciane Velloso, Lício Augusto Fagundes, João José Salas, Azucena Leal, Raquel Franco J Transl Med Research BACKGROUND: Crohn’s disease (CD) is a multifactorial disease characterized by chronic intestinal inflammation. The increased visceral adiposity near the affected intestinal area, of which mesenteric adipose tissue (MAT) is the main component, is a feature of CD. Both protective and pathological roles have been attributed to this disease-associated tissue in CD. To understand the contribution of MAT to CD pathophysiology, a molecular and cellular signature of disease-associated MAT in CD patients was provided. METHODS: We performed an observational study with whole transcriptional analysis by RNA sequencing (RNA-seq) of MAT and ileal mucosa from CD patients with active disease and controls. qPCR and immunohistology were performed for validation analysis. RESULTS: RNA-seq identified 17 significantly regulated genes (|FC| > 1.5; FDR < 0.05) in CD-MAT compared to non-IBD controls, with a marked upregulation of plasma cell genes (i.e., IGLL5, MZB1, CD79A, POU2AF1, FCRL5, JCHAIN, DERL3, SDC1, PIM2). A less strict statistical cutoff value (|FC| > 1.5, nominal p ≤ 0.05) yielded a larger list of 651 genes in CD-MAT compared to controls. CD ileum showed the significant regulation compared to control ileum of 849 genes (|FC| > 1.5; FDR < 0.05) or 2654 genes (|FC| > 1.5, nominal p ≤ 0.05). Ingenuity Pathway Analysis revealed the significant regulation of pathways related to T- and B cell functionality in the MAT of CD patients. Despite the differences between the MAT and ileal signatures of CD patients, we identified a subset of 204 genes significantly modulated in both tissues compared to controls. This common signature included genes related to the plasma cell signature. Genes such as S100A8, S100A9 (calprotectin) and IL1B, which are associated with acute inflammatory response, were exclusively regulated in the ileal mucosa of CD disease. In contrast, some genes encoding for lymphocyte receptors such as MS4A1, CD3D and CD79A were exclusively regulated in CD-MAT, exhibiting a different pattern of immune cell activation compared to the ileal mucosa in CD patients. qPCR and immunohistology confirmed the presence of large infiltrates of CD3(+) CD20(+) lymphocytes and CD138(+) plasma cells in CD-MAT. CONCLUSION: Our data strongly supports the role of CD-associated MAT as a site for T-, B- and plasma cell activation, and suggests that it could also act as a reservoir of memory immune responses. BioMed Central 2020-01-30 /pmc/articles/PMC6993458/ /pubmed/32000799 http://dx.doi.org/10.1186/s12967-020-02220-3 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research da Silva, Francesca Aparecida Ramos Pascoal, Lívia Bitencourt Dotti, Isabella Setsuko Ayrizono, Maria de Lourdes Aguilar, Daniel Rodrigues, Bruno Lima Arroyes, Montserrat Ferrer-Picon, Elena Milanski, Marciane Velloso, Lício Augusto Fagundes, João José Salas, Azucena Leal, Raquel Franco Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn’s disease |
title | Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn’s disease |
title_full | Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn’s disease |
title_fullStr | Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn’s disease |
title_full_unstemmed | Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn’s disease |
title_short | Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn’s disease |
title_sort | whole transcriptional analysis identifies markers of b, t and plasma cell signaling pathways in the mesenteric adipose tissue associated with crohn’s disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993458/ https://www.ncbi.nlm.nih.gov/pubmed/32000799 http://dx.doi.org/10.1186/s12967-020-02220-3 |
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