Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Sci Immunol. 2022 Mar 18;7(69):eabg9296. doi: 10.1126/sciimmunol.abg9296.
Asthma is a chronic inflammatory lung disease with intermittent flares predominately mediated through memory T cells. Yet, the identity of long-term memory cells that mediate allergic recall responses is not well defined. In this report, using a mouse model of chronic allergen exposure followed by an allergen-free rest period, we characterized a subpopulation of CD4 T cells that secreted IL-9 as an obligate effector cytokine. IL-9-secreting cells had a resident memory T cell phenotype, and blocking IL-9 during a recall challenge or deleting IL-9 from T cells significantly diminished airway inflammation and airway hyperreactivity. T cells secreted IL-9 in an allergen recall-specific manner, and secretion was amplified by IL-33. Using scRNA-seq and scATAC-seq, we defined the cellular identity of a distinct population of T cells with a proallergic cytokine pattern. Thus, in a recall model of allergic airway inflammation, IL-9 secretion from a multicytokine-producing CD4 T cell population was required for an allergen recall response.
哮喘是一种慢性炎症性肺部疾病，其间歇性发作主要通过记忆 T 细胞介导。然而，介导过敏再发反应的长期记忆细胞的身份尚未明确。在本报告中，我们使用慢性变应原暴露后无变应原休息期的小鼠模型，对分泌白细胞介素 9（IL-9）的 CD4 T 细胞亚群进行了特征描述，IL-9 是一种必需的效应细胞因子。分泌白细胞介素 9 的细胞具有常驻记忆 T 细胞表型，在回忆性挑战期间阻断白细胞介素 9 或从 T 细胞中删除白细胞介素 9 可显著减轻气道炎症和气道高反应性。T 细胞以变应原回忆特异性方式分泌白细胞介素 9，白细胞介素 33 可放大其分泌。通过 scRNA-seq 和 scATAC-seq，我们定义了具有促过敏细胞因子模式的独特 T 细胞群体的细胞身份。因此，在过敏气道炎症的回忆模型中，多细胞因子产生的 CD4 T 细胞群体分泌白细胞介素 9 是变应原回忆反应所必需的。
