Department of Oncology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Basic Science, YuanDong International Academy Of Life Sciences, Hong Kong, China.
Front Immunol. 2022 Oct 25;13:849341. doi: 10.3389/fimmu.2022.849341. eCollection 2022.
Ionizing radiation (IR) has been widely used in the diagnosis and treatment of clinical diseases, with radiation therapy (RT) being particularly rapid, but it can induce "bystander effects" that lead to biological responses in non-target cells after their neighboring cells have been irradiated. To help clarify how radiotherapy induces these effects, To help clarify how radiotherapy induces these effects, we analyzed single-cell RNA sequencing data from irradiated intestinal tissues on day 1 (T1 state), day 3 (T3 state), day 7 (T7 state), and day 14 (T14 state) after irradiation, as well as from healthy intestinal tissues (T0 state), to reveal the cellular level, molecular level, and involvement of different time irradiated mouse intestinal tissues in biological signaling pathways. In addition, changes in immune cell subpopulations and myeloid cell subpopulations after different radiation times were further explored, and gene regulatory networks (GRNs) of these cell subpopulations were constructed. Cellular communication between radiation-specific immune cells was explored by cell-to-cell communication events. The results suggest that radiotherapy trigger changes in immune cell subsets, which then reprogram the immune ecosystem and mediate systemic bystander effects. These radiation-specific immune cells participate in a wide range of cell-to-cell communication events. In particular, radiation-specific CD8+T cells appear to be at the core of communication and appear to persist in the body after recovery from radiotherapy, with enrichment analysis showing that radiation-specific CD8+ T cells are associated with ferroptosis. Thus, radiation-specific CD8+ T cells may be involved in cellular ferroptosis-mediated adverse effects caused by RT.
电离辐射 (IR) 已广泛应用于临床疾病的诊断和治疗，其中放射治疗 (RT) 尤为迅速，但它会诱导“旁观者效应”，即在其相邻细胞受到照射后，非靶细胞会产生生物反应。为了帮助阐明放疗如何诱导这些效应，我们分析了照射后第 1 天（T1 状态）、第 3 天（T3 状态）、第 7 天（T7 状态）和第 14 天（T14 状态）的照射肠道组织以及健康肠道组织（T0 状态）的单细胞 RNA 测序数据，以揭示细胞水平、分子水平以及不同时间照射的小鼠肠道组织在生物信号通路中的参与情况。此外，进一步探讨了不同照射时间后免疫细胞亚群和髓样细胞亚群的变化，并构建了这些细胞亚群的基因调控网络 (GRN)。通过细胞间通信事件探讨了辐射特异性免疫细胞之间的细胞间通信。结果表明，放疗触发免疫细胞亚群的变化，进而重新编程免疫生态系统并介导全身旁观者效应。这些辐射特异性免疫细胞参与广泛的细胞间通信事件。特别是，辐射特异性 CD8+T 细胞似乎处于通信的核心位置，并且在放疗后恢复时似乎在体内持续存在，富集分析表明辐射特异性 CD8+T 细胞与铁死亡有关。因此，辐射特异性 CD8+T 细胞可能参与由 RT 引起的细胞铁死亡介导的不良反应。
