Thompson David A, Wabara Yvonne B, Duran Sarai, Reichenbach Anna, Chen Laura, Collado Kayla, Yon Changsuek, Greally DMed John M, Rastogi Deepa
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA.
Children's National Hospital, George Washington University, Washington, DC, USA.
Sci Rep. 2025 Feb 26;15(1):6844. doi: 10.1038/s41598-025-88423-4.
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.
小儿肥胖相关哮喘的特征为非特应性辅助性T细胞1（Th1）炎症和类固醇抵抗。CD4 + T细胞中CDC42上调是Th1炎症的基础，但尚不清楚CDC42上调的CD4 + T细胞亚型及其对类固醇抵抗的作用。与健康体重哮喘、单纯肥胖和健康体重对照组相比，肥胖哮喘CD4 + T细胞的单细胞转录组学显示，在由幼稚和中央记忆T细胞组成的3个簇中CDC42上调，这与由效应T细胞组成的富含Th1反应的簇不同。在CDC42上调和Th1反应的簇中，编码糖皮质激素受体的NR3C1下调，而编码NLRP3炎性小体的基因上调。这些簇中的保守基因与肥胖哮喘患者的肺功能缺陷相关。这些发现表明，在肥胖哮喘中，几种不同的CD4 + T细胞亚型被编程为CDC42上调、Th1炎症和类固醇抵抗，并共同促成肥胖哮喘表型。
