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A Single Cell Approach to Identify the Role of IL-9 Secreting Tissue-Resident CD4+ T Cells in Allergic Airway Recall Responses

The Journal of Immunology(2020)

Indiana Univ Sch Med

Cited 0|Views26
Abstract
Allergic asthma is a chronic intermittent inflammatory lung disease where patients experience relatively few symptoms between exacerbations precipitated by allergen-challenge of allergic memory responses. Allergen-specific CD4+ T cells are believed to be a major mediator of allergic memory responses through the production of type 2 cytokines including IL-4, IL-5, IL-13 and IL-9. Recently, tissue-resident memory (Trm) cells have been identified in peripheral tissues that mediate mucosal barrier immunity. However, the precise role of Trm CD4+ T cells in allergic exacerbations is not clearly defined. In studies to examine the role of IL-9 in allergen-specific Trm responses to Aspergillus fumigatus we observed that all IL-9-secreting T cells had a resident memory phenotype. Inhibition of circulating T cells by administering FTY720 in the last month of rest, diminished the total CD4 T cells population in the lung, while the Th9 cells remained stable. Blockade of IL-9 prior to recall challenge phase reduced overall allergic lung inflammation as assessed both by flow cytometry and single cell RNA-seq. Within eight hours after challenge, IL-9 is one of the top genes identified by scRNA-seq that distinguishes ST2+ and ST2− CD4+ T cell populations in the lung. Using IL-9-reporter mice we also compared gene expression in isolated IL-9+ T cells and other type 2 T cells. These findings demonstrate that IL-9-producing Trms play an important role in mediating allergic memory responses. IL-9 could be a promising therapeutic target specifically in patients showing symptoms of intermittent allergic response.
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要点】:本研究揭示了分泌IL-9的 tissue-resident CD4+ T 细胞在过敏气道回忆反应中的关键作用,并指出IL-9可能成为间歇性过敏反应患者的潜在治疗靶点。

方法】:通过流式细胞术、单细胞RNA测序以及IL-9报告小鼠等方法研究IL-9分泌T细胞在过敏反应中的作用。

实验】:在给予FTY720抑制循环T细胞后,观察肺中CD4 T细胞的变化,并通过阻断IL-9以及使用IL-9报告小鼠分析IL-9对过敏炎症的影响,实验使用了Aspergillus fumigatus作为过敏原,数据集名称未提及。结果显示IL-9是区分ST2+和ST2- CD4+ T细胞的关键基因之一。