Multiplatform Single-Cell Analysis Identifies Immune Cell Types Enhanced in Pulmonary Fibrosis.
Multiplatform Single-Cell Analysis Identifies Immune Cell Types Enhanced in Pulmonary Fibrosis.
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多平台单细胞分析可识别肺纤维化中增强的免疫细胞类型。
DOI：
10.1165/rcmb.2021-0418oc
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发表时间：
2022
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
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作者：
Serezani,AnaPM;Pascoalino,BrunoD;Bazzano,JuliaMR;Vowell,KatherineN;Tanjore,Harikrishna;Taylor,ChaseJ;Calvi,CarlaL;McCall,AScott;Bacchetta,MatthewD;Shaver,CiaraM;Ware,LorraineB;Salisbury,MargaretL;Banovich,NicholasE;
免疫细胞与特发性肺纤维化（IPF）有关，但这些细胞的表型和效应机制仍不完全。我们进行了大量细胞计数来定量12名IPF患者和15名无慢性肺病的器官供体的肺中的免疫细胞亚群，并使用现有的单细胞RNA测序数据来研究IPF中过度表达的免疫细胞的转录谱。在髓样细胞中，我们发现IPF中肺泡巨噬细胞（AMIs）和树突状细胞（DC）以及单核细胞衍生的DC亚群数量增加。相比之下，IPF中单核细胞样细胞和间质巨噬细胞减少。转录组学分析鉴定了来自IPF的AM和DC中IFN-γ应答途径的富集，以及DC中的抗原加工和AM中的吞噬作用。在T细胞中，我们确定了IPF中增加的三种记忆T细胞亚群，包括CD 4+和CD 8+驻留记忆T细胞（TRM）和CD 8+效应记忆细胞。在IPF中，对IFN-γ途径的应答在CD 4 TRM和CD 8 TRM细胞中富集，同时存在T细胞活化和免疫应答调节信号传导途径。与对照受试者相比，IPF肺中存在增加的AM、DC和记忆T细胞。在IPF中，这些细胞具有活化特征，表明肺中IFN-γ信号传导增加和适应性免疫上调。总之，这些研究突出了IPF免疫发病机制的关键特征。
Immune cells have been implicated in idiopathic pulmonary fibrosis (IPF), but the phenotypes and effector mechanisms of these cells remain incompletely characterized. We performed mass cytometry to quantify immune cell subsets in lungs of 12 patients with IPF and 15 organ donors without chronic lung disease and used existing single-cell RNA-sequencing data to investigate transcriptional profiles of immune cells overrepresented in IPF. Among myeloid cells, we found increased numbers of alveolar macrophages (AMØs) and dendritic cells (DCs) in IPF, as well as a subset of monocyte-derived DCs. In contrast, monocyte-like cells and interstitial macrophages were reduced in IPF. Transcriptomic profiling identified an enrichment for IFN-γ response pathways in AMØs and DCs from IPF, as well as antigen processing in DCs and phagocytosis in AMØs. Among T cells, we identified three subsets of memory T cells that were increased in IPF, including CD4+and CD8+resident memory T cells (TRM) and CD8+effector memory cells. The response to the IFN-γ pathway was enriched in CD4 TRMand CD8 TRMcells in IPF, together with T cell activation and immune response–regulating signaling pathways. Increased AMØs, DCs, and memory T cells were present in IPF lungs compared with control subjects. In IPF, these cells possess an activation profile indicating increased IFN-γ signaling and upregulation of adaptive immunity in the lungs. Together, these studies highlight critical features of the immunopathogenesis of IPF.