Role of a novel immune modulating DDR2-expressing population in silica-induced pulmonary fibrosis
Role of a novel immune modulating DDR2-expressing population in silica-induced pulmonary fibrosis
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DOI：
10.1371/journal.pone.0180724
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发表时间：
2017-07-10
期刊：
影响因子：
3.7
通讯作者：
LaRue, Amanda C.
中科院分区：
文献类型：
--
作者：
McDonald, Lindsay T.;Johnson, Sara D.;LaRue, Amanda C.
与慢性吸入颗粒暴露相关的微损伤与免疫反应的激活有关，并被认为有助于纤维化疾病的进展。在肺环境中，我们之前已经证明了循环成纤维细胞前体（CFPs）的异质群体，其由泛白细胞标志物CD45和胶原受体盘状蛋白结构域受体-2 （DDR2）的表达定义。该群体来源于造血干细胞，表达胶原蛋白，并在体外具有成纤维形态。在此，我们展示了表达免疫标记CD11b、CD11c和主要组织相容性复合体II （MHC II）的CFPs的一个新子集。在二氧化硅诱导的肺纤维化动物中，CFP群体倾向于这种免疫标记表达亚群。数据表明，该CFP亚群上调共刺激分子和MHC II表达，以响应体内二氧化硅诱导的纤维化。在功能上，这个群体被证明可以促进T细胞偏离Th1反应，向促炎症的方向倾斜。这些研究代表了在暴露诱导的肺纤维化模型中表达CFP亚群的新型免疫标记物的首次直接流式细胞术和功能评估。阐明这个CFP亚群的作用可以增强我们对在肺-宿主界面介导暴露的复杂免疫平衡的理解，并可能成为治疗暴露诱导肺纤维化的一个有价值的靶点。
Micro-injuries associated with chronic inhaled particle exposures are linked with activation of the immune response and are thought to contribute to progression of fibrotic disease. In the pulmonary environment, we have previously demonstrated a heterogeneous population of circulating fibroblast precursors (CFPs), which are defined by expression of the pan-leukocyte marker CD45 and the collagen receptor, discoidin domain receptor-2 (DDR2). This population is derived from the hematopoietic stem cell, expresses collagen, and has a fibro-blastic morphology in vitro. Herein, we demonstrate a novel subset of CFPs expressing immune markers CD11b, CD11c, and major histocompatibility complex II (MHC II). The CFP population was skewed toward this immune marker expressing subset in animals with silica-induced pulmonary fibrosis. Data indicate that this CFP subset upregulates co-stimulatory molecules and MHC II expression in response to silica-induced fibrosis in vivo. Functionally, this population was shown to promote T cell skewing away from a Th1 response and toward a pro-inflammatory profile. These studies represent the first direct flow cytometric and functional evaluation of the novel immune marker expressing CFP subset in an exposure-induced model of pulmonary fibrosis. Elucidating the role of this CFP subset may enhance our understanding of the complex immune balance critical to mediating exposures at the pulmonary-host interface and may be a valuable target for the treatment of exposure-induced pulmonary fibrosis.