Beijing Institute of Radiation Medicine, Beijing, China.
Department of Rehabilitation Medicine, Eighth Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Front Immunol. 2022 Jul 27;13:941976. doi: 10.3389/fimmu.2022.941976. eCollection 2022.
Radiation-induced lung injury (RILI) is the most common complication associated with chest tumors, such as lung and breast cancers, after radiotherapy; however, the pathogenic mechanisms are unclear. Single-cell RNA sequencing has laid the foundation for studying RILI at the cellular microenvironmental level. This study focused on changes during the acute pneumonitis stage of RILI at the cellular microenvironmental level and investigated the interactions between different cell types.
An acute RILI model in mice and a single-cell transcriptional library were established. Intercellular communication networks were constructed to study the heterogeneity and intercellular interactions among different cell types.
A single-cell transcriptome map was established in a mouse model of acute lung injury. In total, 18,500 single-cell transcripts were generated, and 10 major cell types were identified. The heterogeneity and radiosensitivity of each cell type or subtype in the lung tissues during the acute stage were revealed. It was found that immune cells had higher radiosensitivity than stromal cells. Immune cells were highly heterogeneous in terms of radiosensitivity, while some immune cells had the characteristics of radiation resistance. Two groups of radiation-induced Cd8Mki67 T cells and Cd4Cxcr6 helper T cells were identified. The presence of these cells was verified using immunofluorescence. The ligand-receptor interactions were analyzed by constructing intercellular communication networks. These explained the origins of the cells and revealed that they had been recruited from endothelial cells to the inflammatory site.
This study revealed the heterogeneity of radiosensitivity of different cell types in the lung at the initial stage post irradiation.
放射性肺损伤（RILI）是胸部肿瘤（如肺癌和乳腺癌）放射治疗后最常见的并发症，但发病机制尚不清楚。单细胞 RNA 测序为研究 RILI 在细胞微环境水平上的发病机制奠定了基础。本研究关注 RILI 急性肺炎期细胞微环境水平的细胞变化，并研究不同细胞类型之间的相互作用。
建立了小鼠急性 RILI 模型和单细胞转录组文库。构建细胞间通讯网络，研究不同细胞类型之间的异质性和细胞间相互作用。
建立了小鼠急性肺损伤模型的单细胞转录组图谱。共生成 18500 个单细胞转录本，鉴定出 10 种主要细胞类型。揭示了急性阶段肺组织中每种细胞类型或亚型的异质性和放射敏感性。发现免疫细胞比基质细胞具有更高的放射敏感性。免疫细胞在放射敏感性方面具有高度异质性，而某些免疫细胞具有辐射抗性的特征。鉴定出两组辐射诱导的 Cd8Mki67 T 细胞和 Cd4Cxcr6 辅助 T 细胞。通过免疫荧光验证了这些细胞的存在。通过构建细胞间通讯网络分析配体-受体相互作用。这些解释了细胞的来源，并揭示了它们已从内皮细胞募集到炎症部位。
本研究揭示了照射后肺部不同细胞类型初始阶段放射敏感性的异质性。
