Interleukin-2-Dependent Allergen-Specific Tissue-Resident Memory Cells Drive Asthma.
Interleukin-2-Dependent Allergen-Specific Tissue-Resident Memory Cells Drive Asthma.
复制标题
DOI：
10.1016/j.immuni.2015.11.004
复制
发表时间：
2016-01-19
期刊：
影响因子：
32.4
通讯作者：
Pepper M
中科院分区：
文献类型：
--
作者：
Hondowicz BD;An D;Schenkel JM;Kim KS;Steach HR;Krishnamurty AT;Keitany GJ;Garza EN;Fraser KA;Moon JJ;Altemeier WA;Masopust D;Pepper M
暴露于吸入性过敏原产生辅助性T细胞2（Th 2）CD 4 + T细胞，其有助于与哮喘相关的炎症发作。关于过敏原特异性Th 2记忆细胞及其对气道炎症的作用知之甚少。我们生成试剂以了解对屋尘螨（HDM）过敏原特异性的内源性CD 4 + T细胞如何形成和发挥作用。过敏原暴露后，HDM特异性记忆细胞持续作为淋巴器官中的中央记忆细胞和肺中的组织驻留记忆（Trm）细胞。淋巴细胞迁移的实验性阻断证明肺驻留细胞足以诱导依赖于CD 4 + T细胞的气道高反应性。对致病性Trm细胞分化的研究表明，白细胞介素-2（IL-2）信号传导是驻留所必需的，并指导了组织归巢迁移线索的程序。因此，这些研究鉴定了IL-2依赖性驻留Th 2记忆细胞作为肺过敏反应的驱动者。
Exposure to inhaled allergens generates T helper 2 (Th2) CD4+ T cells that contribute to episodes of inflammation associated with asthma. Little is known about allergen-specific Th2 memory cells and their contribution to airway inflammation. We generated reagents to understand how endogenous CD4+ T cells specific for a house dust mite (HDM) allergen form and function. After allergen exposure, HDM-specific memory cells persisted as central memory cells in the lymphoid organs and tissue resident memory (Trm) cells in the lung. Experimental blockade of lymphocyte migration demonstrated that lung resident cells were sufficient to induce airway hyper-responsiveness, which depended upon CD4+ T cells. Investigation into the differentiation of pathogenic Trm cells revealed that interleukin-2 (IL-2) signaling was required for residency and directed a program of tissue homing migrational cues. These studies thus identify IL-2-dependent resident Th2 memory cells as drivers of lung allergic responses.