Differential Regulation of Interferon Signaling Pathways in CD4+ T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype.
Fahd AlhamdanLeigh Matthew MarshFrauke PedersenBilal Alashkar AlhamweClemens ThölkenPetra Ina PfefferleThomas BahmerTimm GreulichDaniel P PotaczekHolger GarnPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- lung function
- weight loss
- chronic obstructive pulmonary disease
- metabolic syndrome
- body mass index
- weight gain
- type diabetes
- peripheral blood
- allergic rhinitis
- insulin resistance
- adipose tissue
- rna seq
- dendritic cells
- single cell
- bariatric surgery
- cystic fibrosis
- signaling pathway
- genome wide
- high fat diet induced
- oxidative stress
- ejection fraction
- skeletal muscle
- prognostic factors
- genome wide identification
- copy number
- long non coding rna
- patient reported outcomes
- drug induced
- atopic dermatitis