Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, United States.
Elife. 2022 Sep 29;11:e63296. doi: 10.7554/eLife.63296.
In allergic asthma, allergen inhalation leads to local Th2 cell activation and peribronchial inflammation. However, the mechanisms for local antigen capture and presentation remain unclear. By two-photon microscopy of the mouse lung, we established that soluble antigens in the bronchial airway lumen were efficiently captured and presented by a population of CD11c interstitial macrophages with high CX3CR1-GFP and MHC class II expression. We refer to these cells as Bronchus-Associated Macrophages (BAMs) based on their localization underneath the bronchial epithelium. BAMs were enriched in collagen-rich regions near some airway branchpoints, where inhaled antigens are likely to deposit. BAMs engaged in extended interactions with effector Th2 cells and promoted Th2 cytokine production. BAMs were also often in contact with dendritic cells (DCs). After exposure to inflammatory stimuli, DCs migrated to draining lymph nodes, whereas BAMs remained lung resident. We propose that BAMs act as local antigen presenting cells in the lung and also transfer antigen to DCs.
在过敏性哮喘中,过敏原吸入会导致局部 Th2 细胞活化和支气管周围炎症。然而,局部抗原捕获和呈递的机制仍不清楚。通过对小鼠肺部的双光子显微镜观察,我们发现支气管气道腔中的可溶性抗原可被一群表达高 CX3CR1-GFP 和 MHC Ⅱ类的 CD11c 间质巨噬细胞有效捕获和呈递。我们根据它们在支气管上皮下的定位,将这些细胞称为支气管相关巨噬细胞(BAMs)。BAMs 在富含胶原的气道分支点附近的区域富集,吸入的抗原可能在此沉积。BAMs 与效应性 Th2 细胞进行了广泛的相互作用,并促进了 Th2 细胞因子的产生。BAMs 也经常与树突状细胞(DCs)接触。暴露于炎症刺激后,DC 迁移到引流淋巴结,而 BAMs 仍留在肺部。我们提出,BAMs 作为肺部的局部抗原呈递细胞发挥作用,并且还将抗原转移给 DCs。
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