Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma

Document Type

Journal Article

Publication Date

2-26-2025

Journal

Scientific reports

Volume

15

Issue

1

DOI

10.1038/s41598-025-88423-4

Keywords

Asthma; CD4 + T cells; Children; Obesity

Abstract

Pediatric obesity-related asthma is characterized by non-atopic T helper 1 (Th1) inflammation and steroid resistance. CDC42 upregulation in CD4 + T cells underlies Th1 inflammation but the CD4 + T cell subtype(s) with CDC42 upregulation and their contribution to steroid resistance are not known. Compared to healthy-weight asthma, obesity-alone and healthy-weight controls, single-cell transcriptomics of obese asthma CD4 + T cells revealed CDC42 upregulation in 3 clusters comprised of naïve and central memory T cells, which differed from the cluster enriched for Th1 responses that was comprised of effector T cells. NR3C1, coding for the glucocorticoid receptor, was downregulated, while genes coding for NLRP3 inflammasome were upregulated, in clusters with CDC42 upregulation and Th1 responses. Conserved genes in these clusters correlated with pulmonary function deficits in obese asthma. These findings suggest that several distinct CD4 + T cell subtypes are programmed in obese asthma for CDC42 upregulation, Th1 inflammation, and steroid resistance, and together contribute to the obese asthma phenotype.

Department

Pediatrics

Link to Full Text

Share

COinS