Asthma comprises heterogeneous clinical subtypes driven by diverse pathophysiological mechanisms. We characterized the modulation of the inflammatory environment with the phenotype, gene expression, and function of helper CD4 T cells among acutely exacerbated and stable asthma patients. Systemic Th2 immune deviation (IgE and Th2 cytokines) and inflammation (IL-6, CRP) were associated with increased Th17 cells during acute asthma. Th2/Th17 cell differentiation during acute asthma was regulated by the enhanced expression of transcription factors (c-MAF, IRF-4). The development of pathogenic Th2 cells during acute asthma was characterized by the secretion of inflammatory cytokines coupled with Th2 molecules and PPARγ expression. The acquisition of CD15S, CD39, CD101, and CCR4 contributed to the increased heterogeneity of Regulatory T cells during asthma. Two clusters were derived from above cytokines, CD4 T cell phenotypes, and clinical data. Cluster 1, characterized by high eosinophils, Th2 and ILC2 frequencies, and higher exacerbation rates, may represent Th2-high subtype. Cluster 2 represents a more complex subtype; it is constituted by higher neutrophils or Th17 frequencies, higher inhaled corticosteroids dose and poor asthma control. In conclusion, we characterized systematically and longitudinally Th2-high and non-Th2 asthma subtypes and the heterogeneity of CD4 T cells in stable and acute asthma.

中文翻译：

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急性和稳定过敏性哮喘期间辅助性 CD4 T 细胞的动力学。

哮喘包括由不同病理生理机制驱动的异质临床亚型。我们通过表型、基因表达和辅助性 CD4 T 细胞在急性加重和稳定的哮喘患者中的功能对炎症环境的调节进行了表征。全身性 Th2 免疫偏差（IgE 和 Th2 细胞因子）和炎症（IL-6、CRP）与急性哮喘期间 Th17 细胞增加有关。急性哮喘期间 Th2/Th17 细胞分化受转录因子（c-MAF、IRF-4）表达增强的调节。急性哮喘期间致病性 Th2 细胞的发展以炎性细胞因子的分泌以及 Th2 分子和 PPARγ 的表达为特征。CD15S、CD39、CD101、和 CCR4 导致哮喘期间调节性 T 细胞的异质性增加。两个簇来自上述细胞因子、CD4 T 细胞表型和临床数据。聚类 1 以高嗜酸性粒细胞、Th2 和 ILC2 频率以及较高的恶化率为特征，可能代表 Th2-high 亚型。集群 2 代表更复杂的子类型；它由较高的中性粒细胞或 Th17 频率、较高的吸入皮质类固醇剂量和较差的哮喘控制构成。总之，我们系统地和纵向地表征了 Th2 高和非 Th2 哮喘亚型以及稳定期和急性哮喘中 CD4 T 细胞的异质性。可能代表 Th2-high 亚型。集群 2 代表更复杂的子类型；它由较高的中性粒细胞或 Th17 频率、较高的吸入皮质类固醇剂量和较差的哮喘控制构成。总之，我们系统地和纵向地表征了 Th2 高和非 Th2 哮喘亚型以及稳定期和急性哮喘中 CD4 T 细胞的异质性。可能代表 Th2-high 亚型。集群 2 代表更复杂的子类型；它由较高的中性粒细胞或 Th17 频率、较高的吸入皮质类固醇剂量和较差的哮喘控制构成。总之，我们系统地和纵向地表征了 Th2 高和非 Th2 哮喘亚型以及稳定期和急性哮喘中 CD4 T 细胞的异质性。