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 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.

Automated summary

In this study, RNA sequencing was conducted on peripheral blood CD4(+) T cells from obese non-atopic asthmatic adults, non-obese non-atopic asthmatic adults, and healthy controls. The results showed specific activation of interferon-related signaling pathways in obese asthmatics, while gap junction and GPCR ligand binding pathways were enriched in both asthma groups. Additionally, markers for obesity genes were upregulated in CD4(+) T cells from obese asthmatics, indicating potential novel targets for stratified therapeutic approaches.