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

Int J Mol Sci. 2021 Sep 20;22(18):10144. doi: 10.3390/ijms221810144.


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.

Keywords: CD4+ T cells; asthma phenotypes; low type-2 asthma; obesity; transcriptomics.

MeSH terms

  • Adult
  • Asthma / complications
  • Asthma / metabolism*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Female
  • Humans
  • Interferons / metabolism*
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / metabolism*
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction*


  • Receptors, G-Protein-Coupled
  • Interferons