McDonald Lindsay T, Johnson Sara D, Russell Dayvia L, Young M Rita I, LaRue Amanda C
Research Services, Ralph H. Johnson VA Medical Center, Charleston, South Carolina, United States of America.
The Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
PLoS One. 2017 Jul 10;12(7):e0180724. doi: 10.1371/journal.pone.0180724. eCollection 2017.
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 fibroblastic 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.
与慢性吸入颗粒物暴露相关的微损伤与免疫反应的激活有关，并被认为会促进纤维化疾病的进展。在肺部环境中，我们之前已经证明了循环成纤维细胞前体（CFP）的异质性群体，它们由泛白细胞标志物CD45和胶原蛋白受体盘状结构域受体-2（DDR2）的表达所定义。这个群体来源于造血干细胞，表达胶原蛋白，并且在体外具有成纤维细胞形态。在此，我们证明了一个表达免疫标志物CD11b、CD11c和主要组织相容性复合体II（MHC II）的新型CFP亚群。在二氧化硅诱导的肺纤维化动物中，CFP群体偏向于这个表达免疫标志物的亚群。数据表明，这个CFP亚群在体内对二氧化硅诱导的纤维化反应中上调共刺激分子和MHC II的表达。在功能上，这个群体被证明会促进T细胞从Th1反应转向促炎表型。这些研究代表了在暴露诱导的肺纤维化模型中对表达新型免疫标志物的CFP亚群进行的首次直接流式细胞术和功能评估。阐明这个CFP亚群的作用可能会增强我们对在肺-宿主界面介导暴露至关重要的复杂免疫平衡的理解，并且可能是治疗暴露诱导的肺纤维化的一个有价值的靶点。
