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Differential Regulation of Interferon Signaling Pathways in CD4 + T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype.

Authors :
Alhamdan F
Marsh LM
Pedersen F
Alhamwe BA
Thölken C
Pfefferle PI
Bahmer T
Greulich T
Potaczek DP
Garn H
Source :
International journal of molecular sciences [Int J Mol Sci] 2021 Sep 20; Vol. 22 (18). Date of Electronic Publication: 2021 Sep 20.
Publication Year :
2021

Abstract

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 <superscript>+</superscript> 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 <superscript>+</superscript> 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.

Details

Language :
English
ISSN :
1422-0067
Volume :
22
Issue :
18
Database :
MEDLINE
Journal :
International journal of molecular sciences
Publication Type :
Academic Journal
Accession number :
34576307
Full Text :
https://doi.org/10.3390/ijms221810144