Th2-TRMs Maintain Life-Long Allergic Memory in Experimental Asthma in Mice
Th2-TRMs Maintain Life-Long Allergic Memory in Experimental Asthma in Mice
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DOI：
10.3389/fimmu.2019.00840
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发表时间：
2019-04-24
影响因子：
7.3
通讯作者：
Epstein, Michelle M.
中科院分区：
文献类型：
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作者：
Bosnjak, Berislav;Kazemi, Sahar;Epstein, Michelle M.
过敏性哮喘是一种影响呼吸道的慢性炎症性缓解性疾病。在实验性变态反应性哮喘(EAA)诱导后，小鼠体内的长寿命变应原特异性记忆CD4(+)T辅助细胞2(Th2)细胞在肺中持续存在2年以上。为了进一步了解肺Th2记忆细胞，我们跟踪了健康小鼠脾和肺中的CD4+T细胞，通过急性EAA的启动、恢复(缓解)和过敏原诱导的疾病复发。我们鉴定了一个肺CD3(+)CD4(+)细胞亚群，它表达CD44(Hi)CD62L(-)CD69(+)ST2(+)，产生Th2细胞因子，并介导过敏原诱导的疾病复发，尽管接受FTY720和抗CD4抗体治疗。这些细胞在小鼠的一生中(>；665天)驻留在肺组织中，代表着长寿的致病Th2组织驻留记忆细胞(T-RMS)，在肺中维持“过敏性记忆”。我们推测，这些数据暗示患者肺中的人类Th2-T-RMS哨兵对吸入的过敏原有快速反应并诱导哮喘发作，针对这些细胞的治疗方法可能为过敏性哮喘患者提供缓解。
Allergic asthma is a chronic inflammatory remitting-relapsing disease affecting the airways. Long-lived allergen-specific memory CD4(+) T helper 2 (Th2) cells in mice persist in lungs for more than 2 years after the induction of experimental allergic asthma (EAA). To further understand lung Th2 memory cells, we tracked CD4+ T cells in spleen and lungs from healthy mice, through the initiation of acute EAA, recovery (remission), and allergen-induced disease relapse. We identified a lung CD3(+) CD4(+) cell subset that expresses CD44(hi)CD62L(-)CD69(+)ST2(+), produces Th2 cytokines, and mediates allergen-induced disease relapse despite treatment with FTY720 and anti-CD4 antibody. These cells reside in the lung tissue for the lifetime of mice (>665 days) and represent long-lived pathogenic Th2 tissue resident memory cells (T-RMs) that maintain "allergic memory" in lung. We speculate that these data implicate that human Th2-T-RMs sentinels in lungs of patients are poised to rapidly respond to inhaled allergen and induce asthma attacks and that therapeutic approaches targeting these cells may provide relief to patients with allergic asthma.