Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center, Medical Faculty, Philipps University of Marburg, D-35043 Marburg, Germany.
Ludwig Boltzmann Institute for Lung Vascular Research, A-8010 Graz, Austria.
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.
在个性化医学时代，急需深入了解导致疾病表型（如肥胖相关哮喘等哮喘表型）存在差异的分子机制。从 10 名肥胖、非特应性哮喘成年患者（BMI 为 36.67 ± 6.90）、10 名非肥胖、非特应性哮喘成年患者（BMI 为 23.88 ± 2.73）和 10 名 BMI 正常的健康对照者中抽取外周血。所有哮喘患者均根据选择性临床参数被认为代表低 2 型哮喘表型。对外周血 CD4 T 细胞进行 RNA 测序（RNA-Seq）。与健康对照组相比，两组哮喘患者中有数千个差异表达基因。肥胖哮喘患者中与 IFN 相关信号通路相关的 IFN 刺激基因的表达受到特异性影响，而间隙连接和 G 蛋白偶联受体（GPCR）配体结合途径在两组哮喘患者中均富集。此外，与另外两组相比，肥胖哮喘患者 CD4 T 细胞中的肥胖基因标志物也上调。此外，上述三个途径的富集基因与各种实验室和临床参数表现出独特的相关模式。IFN 相关信号和病毒感染途径的特异性激活可能为肥胖相关低 2 型哮喘表型发展相关的分子机制提供新的视角，这是开发新的分层治疗方法的重要一步。
