Apoptotic Cell-Directed Resolution of Lung Inflammation Requires Myeloid αv Integrin-Mediated Induction of Regulatory T Lymphocytes.
Apoptotic Cell-Directed Resolution of Lung Inflammation Requires Myeloid αv Integrin-Mediated Induction of Regulatory T Lymphocytes.
复制标题
肺部炎症的凋亡细胞定向解决需要骨髓αv整合素介导的调节性T淋巴细胞的诱导。
DOI：
10.1016/j.ajpath.2020.02.010
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Savill,John
中科院分区：
文献类型：
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作者：
Zhang,Ailiang;Lacy-Hulbert,Adam;Anderton,Stephen;Haslett,Christopher;Savill,John
气管内灌注凋亡细胞可增强实验性肺炎症的消退，其机制尚不完全清楚。我们报道，这种干预诱导功能调节性T淋巴细胞（Tregs）在小鼠肺实验性炎症气管内给药脂多糖。选择性耗竭表明，Tregs对于最大限度地提高凋亡细胞定向的分辨率是必要的，并且过继性转移额外的Tregs足以在不给予凋亡细胞的情况下促进分辨率。经气管内灌注后，大多数CD11c+CD103+骨髓树突状细胞中有标记的凋亡细胞迁移到纵隔引流淋巴结，并携带迁移和免疫调节标志物，包括CCR7和β8整合素（ITGB8）表达增加。在髓系中缺失αv整合素以减少CD103+树突状细胞对死亡细胞的吞噬作用的小鼠中，外源性凋亡细胞不能诱导转化生长因子-β1的表达或Treg的积累，也不能增强脂多糖诱导的肺部炎症的消退。我们得出结论，在小鼠肺中，髓系吞噬细胞遇到凋亡细胞时，可以利用αv整合素介导的机制诱导Tregs并增强急性炎症的消退。
Intratracheal instillation of apoptotic cells enhances resolution of experimental lung inflammation by incompletely understood mechanisms. We report that this intervention induces functional regulatory T lymphocytes (Tregs) in mouse lung experimentally inflamed by intratracheal administration of lipopolysaccharide. Selective depletion demonstrated that Tregs were necessary for maximal apoptotic cell–directed enhancement of resolution, and adoptive transfer of additional Tregs was sufficient to promote resolution without administering apoptotic cells. After intratracheal instillation, labeled apoptotic cells were observed in most CD11c+CD103+myeloid dendritic cells migrating to mediastinal draining lymph nodes and bearing migratory and immunoregulatory markers, including increased CCR7 and β8 integrin (ITGB8) expression. In mice deleted for αv integrin in the myeloid line to reduce phagocytosis of dying cells by CD103+dendritic cells, exogenous apoptotic cells failed to induce transforming growth factor-β1 expression or Treg accumulation and failed to enhance resolution of lipopolysaccharide-induced lung inflammation. We conclude that in murine lung, myeloid phagocytes encountering apoptotic cells can deploy αv integrin–mediated mechanisms to induce Tregs and enhance resolution of acute inflammation.