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Differential Regulation of Interferon Signaling Pathways in CD4(+) T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype
In the era of personalized medicine, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as asthma phenotypes including obesity-associated asthma, are urgently needed. Peripheral blood was drawn from 10 obese, non-atopic asthmatic adults with a high body...
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/PMC8469911/ https://www.ncbi.nlm.nih.gov/pubmed/34576307 http://dx.doi.org/10.3390/ijms221810144 |
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author | Alhamdan, Fahd Marsh, Leigh M. Pedersen, Frauke Alhamwe, Bilal Alashkar Thölken, Clemens Pfefferle, Petra Ina Bahmer, Thomas Greulich, Timm Potaczek, Daniel P. Garn, Holger |
author_facet | Alhamdan, Fahd Marsh, Leigh M. Pedersen, Frauke Alhamwe, Bilal Alashkar Thölken, Clemens Pfefferle, Petra Ina Bahmer, Thomas Greulich, Timm Potaczek, Daniel P. Garn, Holger |
author_sort | Alhamdan, Fahd |
collection | PubMed |
description | In the era of personalized medicine, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as asthma phenotypes including obesity-associated asthma, are urgently needed. Peripheral blood was drawn from 10 obese, non-atopic asthmatic adults with a high body mass index (BMI; 36.67 ± 6.90); 10 non-obese, non-atopic asthmatic adults with normal BMI (23.88 ± 2.73); and 10 healthy controls with normal BMI (23.62 ± 3.74). All asthmatic patients were considered to represent a low type-2 asthma phenotype according to selective clinical parameters. RNA sequencing (RNA-Seq) was conducted on peripheral blood CD4(+) T cells. Thousands of differentially expressed genes were identified in both asthma groups compared with heathy controls. The expression of interferon (IFN)-stimulated genes associated with IFN-related signaling pathways was specifically affected in obese asthmatics, while the gap junction and G protein-coupled receptor (GPCR) ligand binding pathways were enriched in both asthma groups. Furthermore, obesity gene markers were also upregulated in CD4(+) T cells from obese asthmatics compared with the two other groups. Additionally, the enriched genes of the three abovementioned pathways showed a unique correlation pattern with various laboratory and clinical parameters. The specific activation of IFN-related signaling and viral infection pathways might provide a novel view of the molecular mechanisms associated with the development of the low type-2 obesity-associated asthma phenotype, which is a step ahead in the development of new stratified therapeutic approaches. |
format | Online Article Text |
id | pubmed-8469911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84699112021-09-27 Differential Regulation of Interferon Signaling Pathways in CD4(+) T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype Alhamdan, Fahd Marsh, Leigh M. Pedersen, Frauke Alhamwe, Bilal Alashkar Thölken, Clemens Pfefferle, Petra Ina Bahmer, Thomas Greulich, Timm Potaczek, Daniel P. Garn, Holger Int J Mol Sci Article In the era of personalized medicine, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as asthma phenotypes including obesity-associated asthma, are urgently needed. Peripheral blood was drawn from 10 obese, non-atopic asthmatic adults with a high body mass index (BMI; 36.67 ± 6.90); 10 non-obese, non-atopic asthmatic adults with normal BMI (23.88 ± 2.73); and 10 healthy controls with normal BMI (23.62 ± 3.74). All asthmatic patients were considered to represent a low type-2 asthma phenotype according to selective clinical parameters. RNA sequencing (RNA-Seq) was conducted on peripheral blood CD4(+) T cells. Thousands of differentially expressed genes were identified in both asthma groups compared with heathy controls. The expression of interferon (IFN)-stimulated genes associated with IFN-related signaling pathways was specifically affected in obese asthmatics, while the gap junction and G protein-coupled receptor (GPCR) ligand binding pathways were enriched in both asthma groups. Furthermore, obesity gene markers were also upregulated in CD4(+) T cells from obese asthmatics compared with the two other groups. Additionally, the enriched genes of the three abovementioned pathways showed a unique correlation pattern with various laboratory and clinical parameters. The specific activation of IFN-related signaling and viral infection pathways might provide a novel view of the molecular mechanisms associated with the development of the low type-2 obesity-associated asthma phenotype, which is a step ahead in the development of new stratified therapeutic approaches. MDPI 2021-09-20 /pmc/articles/PMC8469911/ /pubmed/34576307 http://dx.doi.org/10.3390/ijms221810144 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 Alhamdan, Fahd Marsh, Leigh M. Pedersen, Frauke Alhamwe, Bilal Alashkar Thölken, Clemens Pfefferle, Petra Ina Bahmer, Thomas Greulich, Timm Potaczek, Daniel P. Garn, Holger Differential Regulation of Interferon Signaling Pathways in CD4(+) T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype |
title | Differential Regulation of Interferon Signaling Pathways in CD4(+) T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype |
title_full | Differential Regulation of Interferon Signaling Pathways in CD4(+) T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype |
title_fullStr | Differential Regulation of Interferon Signaling Pathways in CD4(+) T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype |
title_full_unstemmed | Differential Regulation of Interferon Signaling Pathways in CD4(+) T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype |
title_short | Differential Regulation of Interferon Signaling Pathways in CD4(+) T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype |
title_sort | differential regulation of interferon signaling pathways in cd4(+) t cells of the low type-2 obesity-associated asthma phenotype |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469911/ https://www.ncbi.nlm.nih.gov/pubmed/34576307 http://dx.doi.org/10.3390/ijms221810144 |
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