IFN-γ production by innate immune cells is sufficient for development of hypersensitivity pneumonitis
IFN-γ production by innate immune cells is sufficient for development of hypersensitivity pneumonitis
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DOI：
10.1002/eji.200425762
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发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Fitzpatrick, EA
中科院分区：
文献类型：
--
作者：
Nance, S;Cross, R;Fitzpatrick, EA
过敏性肺炎（HP）是一种间质性肺病，在反复暴露于吸入颗粒抗原后发生。该病以淋巴细胞性肺泡炎、肉芽肿形成和纤维化为特征。IFN-γ是HP肉芽肿形成所必需的，因此，我们专注于确定疾病期间IFN-γ的细胞来源。使用HP的直枝多孢菌（SR）动物模型，我们证明了SR暴露后肺中的大多数IFN-γ（+）细胞是中性粒细胞。与同种型Ab处理的小鼠相比，暴露于SR之前Ab介导的小鼠中性粒细胞耗竭导致IFN-γ mRNA和蛋白质水平降低，表明中性粒细胞是HP期间IFN-γ的重要来源。为了确定IFN-γ的T细胞和非T细胞来源对肉芽肿形成的贡献，我们进行了过继转移研究。用IFN-γ（-/-）小鼠的脾细胞重建的RAG-1（-/-）小鼠与用正常脾细胞重建的RAG-1（-/-）小鼠发生类似的肉芽肿。因此，在不存在T细胞IFN-γ产生的情况下，先天免疫细胞IFN-γ产生足以形成肉芽肿。这些结果为HP的发病机制提供了新的见解，并证明了先天免疫细胞对疾病过程的重要贡献。
Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled particulate antigens. The disease is characterized by lymphocytic alveolitis, granuloma formation and fibrosis. IFN-gamma is required for the formation of granulomas in HP, and we therefore focused on identifying the cellular sources of IFN-gamma during the disease. Using the Saccharopolyspora rectivirgula (SR) animal model of HP, we demonstrated that the majority of IFN-gamma(+) cells in the lung following SR exposure are neutrophils. Ab-mediated depletion of neutrophils in mice prior to exposure to SR resulted in a decrease in the level of IFN-gamma mRNA and protein compared to isotype Ab-treated mice, suggesting that neutrophils are an important source of IFN-gamma during HP. To determine the contribution of T and non-T cell sources of IFN-gamma to granuloma formation, we performed adoptive transfer studies. RAG-1(-/-) mice reconstituted with spleen cells from IFN-gamma(-/-) mice developed granulomas similarly to RAG-1(-/-) mice reconstituted with normal spleen cells. Therefore innate immune cell IFN-gamma production in the absence of T cell IFN-gamma production is sufficient for granuloma formation. These results provide new insight into the pathogenesis of HP and demonstrate the important contribution of innate immune cells to the disease process.