PDF(Pubmed)
Abstract：
UNASSIGNED: Schistosomiasis is a common cause of pulmonary hypertension (PH) worldwide. Type 2 inflammation contributes to the development of Schistosoma-induced PH. Specifically, interstitial macrophages (IMs) derived from monocytes play a pivotal role by producing thrombospondin-1 (TSP-1), which in turn activates TGF-β, thereby driving the pathology of PH. Resident and recruited IM subpopulations have recently been identified. We hypothesized that in Schistosoma-PH, one IM subpopulation expresses monocyte recruitment factors, whereas recruited monocytes become a separate IM subpopulation that expresses TSP-1.
UNASSIGNED: Mice were intraperitoneally sensitized and then intravenously challenged with S. mansoni eggs. Flow cytometry on lungs and blood was performed on wildtype and reporter mice to identify IM subpopulations and protein expression. Single-cell RNA sequencing (scRNAseq) was performed on flow-sorted IMs from unexposed and at day 1, 3 and 7 following Schistosoma exposure to complement flow cytometry based IM characterization and identify gene expression.
UNASSIGNED: Flow cytometry and scRNAseq both identified 3 IM subpopulations, characterized by CCR2, MHCII, and FOLR2 expression. Following Schistosoma exposure, the CCR2+ IM subpopulation expanded, suggestive of circulating monocyte recruitment. Schistosoma exposure caused increased monocyte-recruitment ligand CCL2 expression in the resident FOLR2+ IM subpopulation. In contrast, the vascular pathology-driving protein TSP-1 was greatest in the CCR2+ IM subpopulation.
UNASSIGNED: Schistosoma-induced PH involves crosstalk between IM subpopulations, with increased expression of monocyte recruitment ligands by resident FOLR2+ IMs, and the recruitment of CCR2+ IMs which express TSP-1 that activates TGF-β and causes PH.
UNASSIGNED: Mice were intraperitoneally sensitized and then intravenously challenged with S. mansoni eggs. Flow cytometry on lungs and blood was performed on wildtype and reporter mice to identify IM subpopulations and protein expression. Single-cell RNA sequencing (scRNAseq) was performed on flow-sorted IMs from unexposed and at day 1, 3 and 7 following Schistosoma exposure to complement flow cytometry based IM characterization and identify gene expression.
UNASSIGNED: Flow cytometry and scRNAseq both identified 3 IM subpopulations, characterized by CCR2, MHCII, and FOLR2 expression. Following Schistosoma exposure, the CCR2+ IM subpopulation expanded, suggestive of circulating monocyte recruitment. Schistosoma exposure caused increased monocyte-recruitment ligand CCL2 expression in the resident FOLR2+ IM subpopulation. In contrast, the vascular pathology-driving protein TSP-1 was greatest in the CCR2+ IM subpopulation.
UNASSIGNED: Schistosoma-induced PH involves crosstalk between IM subpopulations, with increased expression of monocyte recruitment ligands by resident FOLR2+ IMs, and the recruitment of CCR2+ IMs which express TSP-1 that activates TGF-β and causes PH.
摘要：
■血吸虫病是全球肺动脉高压（PH）的常见原因。2型炎症有助于血吸虫诱导的PH的发展。具体来说,来自单核细胞的间质巨噬细胞（IM）通过产生血小板反应蛋白-1（TSP-1）发挥关键作用，进而激活TGF-β，从而驱动PH的病理。最近已经确定了居民和招募的IM亚群。我们假设在血吸虫PH中，一个IM亚群表达单核细胞募集因子，而募集的单核细胞成为表达TSP-1的单独IM亚群。
■对小鼠进行腹膜内致敏,然后用S.mansoni卵静脉内攻击。对野生型和报告小鼠进行肺和血液的流式细胞术以鉴定IM亚群和蛋白质表达。在血吸虫暴露于基于补体流式细胞术的IM表征和鉴定基因表达后的第1、3和7天对来自未暴露的流动分选的IM进行单细胞RNA测序(scRNAseq)。
■流式细胞术和scRNAseq均鉴定出3个IM亚群，以CCR2、MHCII、和FOLR2表达式。血吸虫暴露后,CCR2+IM亚群扩展，提示循环单核细胞募集。血吸虫暴露导致常驻FOLR2IM亚群中单核细胞募集配体CCL2表达增加。相比之下,血管病理驱动蛋白TSP-1在CCR2+IM亚群中最显著.
■血吸虫诱发的PH涉及IM亚群之间的串扰，随着常驻FOLR2+IM的单核细胞募集配体表达增加，以及表达激活TGF-β并引起PH的TSP-1的CCR2IMs的募集。
■对小鼠进行腹膜内致敏,然后用S.mansoni卵静脉内攻击。对野生型和报告小鼠进行肺和血液的流式细胞术以鉴定IM亚群和蛋白质表达。在血吸虫暴露于基于补体流式细胞术的IM表征和鉴定基因表达后的第1、3和7天对来自未暴露的流动分选的IM进行单细胞RNA测序(scRNAseq)。
■流式细胞术和scRNAseq均鉴定出3个IM亚群，以CCR2、MHCII、和FOLR2表达式。血吸虫暴露后,CCR2+IM亚群扩展，提示循环单核细胞募集。血吸虫暴露导致常驻FOLR2IM亚群中单核细胞募集配体CCL2表达增加。相比之下,血管病理驱动蛋白TSP-1在CCR2+IM亚群中最显著.
■血吸虫诱发的PH涉及IM亚群之间的串扰，随着常驻FOLR2+IM的单核细胞募集配体表达增加，以及表达激活TGF-β并引起PH的TSP-1的CCR2IMs的募集。
