Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice
Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice
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DOI：
10.1172/jci39717
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发表时间：
2009-12-01
影响因子：
15.9
通讯作者：
Bureau, Fabrice
中科院分区：
文献类型：
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作者：
Bedoret, Denis;Wallemacq, Hugues;Bureau, Fabrice
呼吸道持续暴露于无害的空气传播抗原和微生物来源的免疫刺激分子，如LPS。在低浓度下，空气中的LPS可以诱导肺DC驱动的Th 2细胞对无害的吸入抗原的应答，从而促进过敏性哮喘。然而，只有一小部分暴露于环境LIPS的人会患上过敏性哮喘。是什么阻止了大多数人在暴露于LPS时产生肺DC驱动的Th 2应答尚不清楚。在这里，我们已经表明，肺间质巨噬细胞（IM），一个细胞群，没有以前描述的体内功能，防止诱导的Th 2反应在小鼠与LPS和实验无害的空气传播抗原的挑战。发现IM，但不是肺泡巨噬细胞，产生高水平的IL-10，并抑制LPS诱导的成熟和迁移的DC加载与实验无害的空气传播的抗原在IL-10依赖的方式。我们进一步证明，在体内特异性消除IM导致对吸入低剂量LPS的无害空气传播抗原的明显哮喘反应。这项研究揭示了IM在维持呼吸道免疫稳态中的关键作用，并为以下悖论提供了解释：虽然空气中的LPS能够促进肺DCs诱导Th 2应答，但在正常条件下不会引起气道过敏。
The respiratory tract is continuously exposed to both innocuous airborne antigens and immunostimulatory molecules of microbial origin, such as LPS. At low concentrations, airborne LPS can induce a lung DC-driven Th2 cell response to harmless inhaled antigens, thereby promoting allergic asthma. However, only a small fraction of people exposed to environmental LIPS develop allergic asthma. What prevents most people from mounting a lung DC-driven Th2 response upon exposure to LPS is not understood. Here we have shown that lung interstitial macrophages (IMs), a cell population with no previously described in vivo function, prevent induction of a Th2 response in mice challenged with LPS and an experimental harmless airborne antigen. IMs, but not alveolar macrophages, were found to produce high levels of IL-10 and to inhibit LPS-induced maturation and migration of DCs loaded with the experimental harmless airborne antigen in an IL-10-dependent manner. We further demonstrated that specific in vivo elimination of IMs led to overt asthmatic reactions to innocuous airborne antigens inhaled with low doses of LPS. This study has revealed a crucial role for IMs in maintaining immune homeostasis in the respiratory tract and provides an explanation for the paradox that although airborne LPS has the ability to promote the induction of Th2 responses by lung DCs, it does not provoke airway allergy under normal conditions.