组织常驻和循环记忆Th2细胞在过敏性气道疾病中的不同功能
2020/09/18
摘要
记忆 CD4+ Th2型细胞驱动过敏性哮喘，但组织常驻记忆Th2 (Th2 Trm)细胞和循环记忆Th2细胞在体内协同作用的机制尚不清楚。利用屋尘螨(HDM)过敏性哮喘和异种共生模型，我们证明了Th2 Trm细胞和循环记忆Th2细胞执行不同的功能。在HDM再激发时，循环记忆Th2细胞进入肺实质，激起血管周围炎症，促进嗜酸性粒细胞和CD4+ T细胞的招募。与此相反，Th2 Trm细胞在气道附近增殖，诱导黏液上皮化生、气道高反应性和气道嗜酸性粒细胞激活。转录分析显示，Th2 Trm细胞和循环记忆的Th2细胞共享一个核心的Th2基因标记，但也显示不同的转录谱。Th2 Trm细胞表达一种组织适应特征，包括参与调节和与细胞外基质相互作用的基因。我们的研究结果表明，Th2 Trm细胞和循环记忆Th2细胞在功能和转录上是不同的亚群，在促进过敏性气道疾病中发挥独特的作用。
Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease
Rod A Rahimi , Keshav Nepal , Murat Cetinbas, Ruslan I Sadreyev, Andrew D Luster
Abstract
Memory CD4+ T helper type 2 (Th2) cells drive allergic asthma, yet the mechanisms whereby tissue-resident memory Th2 (Th2 Trm) cells and circulating memory Th2 cells collaborate in vivo remain unclear. Using a house dust mite (HDM) model of allergic asthma and parabiosis, we demonstrate that Th2 Trm cells and circulating memory Th2 cells perform nonredundant functions. Upon HDM rechallenge, circulating memory Th2 cells trafficked into the lung parenchyma and ignited perivascular inflammation to promote eosinophil and CD4+ T cell recruitment. In contrast, Th2 Trm cells proliferated near airways and induced mucus metaplasia, airway hyperresponsiveness, and airway eosinophil activation. Transcriptional analysis revealed that Th2 Trm cells and circulating memory Th2 cells share a core Th2 gene signature but also exhibit distinct transcriptional profiles. Th2 Trm cells express a tissue-adaptation signature, including genes involved in regulating and interacting with extracellular matrix. Our findings demonstrate that Th2 Trm cells and circulating memory Th2 cells are functionally and transcriptionally distinct subsets with unique roles in promoting allergic airway disease.
记忆 CD4+ Th2型细胞驱动过敏性哮喘，但组织常驻记忆Th2 (Th2 Trm)细胞和循环记忆Th2细胞在体内协同作用的机制尚不清楚。利用屋尘螨(HDM)过敏性哮喘和异种共生模型，我们证明了Th2 Trm细胞和循环记忆Th2细胞执行不同的功能。在HDM再激发时，循环记忆Th2细胞进入肺实质，激起血管周围炎症，促进嗜酸性粒细胞和CD4+ T细胞的招募。与此相反，Th2 Trm细胞在气道附近增殖，诱导黏液上皮化生、气道高反应性和气道嗜酸性粒细胞激活。转录分析显示，Th2 Trm细胞和循环记忆的Th2细胞共享一个核心的Th2基因标记，但也显示不同的转录谱。Th2 Trm细胞表达一种组织适应特征，包括参与调节和与细胞外基质相互作用的基因。我们的研究结果表明，Th2 Trm细胞和循环记忆Th2细胞在功能和转录上是不同的亚群，在促进过敏性气道疾病中发挥独特的作用。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(J Exp Med. 2020 Sep 7;217(9):e20190865. doi: 10.1084/jem.20190865.)
(J Exp Med. 2020 Sep 7;217(9):e20190865. doi: 10.1084/jem.20190865.)
Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease
Rod A Rahimi , Keshav Nepal , Murat Cetinbas, Ruslan I Sadreyev, Andrew D Luster
Abstract
Memory CD4+ T helper type 2 (Th2) cells drive allergic asthma, yet the mechanisms whereby tissue-resident memory Th2 (Th2 Trm) cells and circulating memory Th2 cells collaborate in vivo remain unclear. Using a house dust mite (HDM) model of allergic asthma and parabiosis, we demonstrate that Th2 Trm cells and circulating memory Th2 cells perform nonredundant functions. Upon HDM rechallenge, circulating memory Th2 cells trafficked into the lung parenchyma and ignited perivascular inflammation to promote eosinophil and CD4+ T cell recruitment. In contrast, Th2 Trm cells proliferated near airways and induced mucus metaplasia, airway hyperresponsiveness, and airway eosinophil activation. Transcriptional analysis revealed that Th2 Trm cells and circulating memory Th2 cells share a core Th2 gene signature but also exhibit distinct transcriptional profiles. Th2 Trm cells express a tissue-adaptation signature, including genes involved in regulating and interacting with extracellular matrix. Our findings demonstrate that Th2 Trm cells and circulating memory Th2 cells are functionally and transcriptionally distinct subsets with unique roles in promoting allergic airway disease.
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