文献类型：期刊文献

英文题名：Regulatory role of RGMb in lung injury promoted by the combination of carbon ion irradiation and anti-PD-1 antibody through Erk1/2 and p38 MAPK pathways

作者：Feng, Shuangwu[1];Luo, Hongtao[2,3];Li, Chengcheng[1];Geng, Yichao[1];Yang, Zhen[2,4];Zhao, Xueshan[1];Wang, Lina[1];Liu, Ruifeng[2,3];Zhang, Yanying[4];Che, Tuanjie[5];Zhang, Qiuning[2,3];Wang, Xiaohu[1,2,3,5]

第一作者：Feng, Shuangwu

通信作者：Wang, XH[1];Zhang, QN[2];Wang, XH[2]

机构：[1]Lanzhou Univ, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China;[2]Chinese Acad Sci, Inst Modern Phys, Lanzhou, Gansu, Peoples R China;[3]Univ Chinese Acad Sci, Beijing, Peoples R China;[4]Gansu Univ Tradit Chinese Med, Lanzhou, Gansu, Peoples R China;[5]Key Lab Funct Genom & Mol Diag Gansu Prov, Lanzhou, Gansu, Peoples R China

第一机构：Lanzhou Univ, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China;[2]corresponding author), Chinese Acad Sci, Inst Modern Phys, Lanzhou, Gansu, Peoples R China.

年份：2024

卷号：691

外文期刊名：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

收录：;Scopus(收录号：2-s2.0-85179063685);WOS:【SCI-EXPANDED(收录号:WOS:001128398700001)】；

基金：This research was funded by the National Key Research and Devel-opment Program of China (No. 2022YFC2401500) , the Science and Technology Plan Project of Chengguan District of Lanzhou (No.2020-2-2-5) , Talent Innovation and Venture Project of Lanzhou City (No. 2021-RC-125; 2020-RC-113) , China Foundation for International Medical Exchange (No. Z-2017-24-2108) , and Lanzhou heavy Ion Accelerator High-end user Project (No. HIR20GY007) .

语种：英文

外文关键词：Anti-PD-1 antibody; Carbon ions; Radiotherapy; Lung injury; Tissue-resident memory T cells; Repulsive guidance molecule b

摘要：The combination of carbon ion radiotherapy and anti-PD-1 antibody represents a new approach to treating thoracic tumors. However, the lung damage caused by this combination therapy may limit its use, and the potential mechanisms for this are worthy of investigation. The objective of this research was to examine the potential involvement of repulsive guidance molecule b (RGMb) in lung damage promoted by the utilization of carbon ion irradiation combined with an anti-PD-1 antibody. The C57BL/6 mice have been randomly separated into four distinct groups: control, anti-PD-1, whole thorax carbon ion irradiation, and irradiation in combination with anti-PD-1 treatment groups (combination group). Detection of pathological changes in lung tissue using HE staining. Detection of pulmonary fibrosis by Masson staining and the hydroxyproline assay. ELISA to detect TNF alpha, TGF-I3, IL-6, and IL-1I3 expression levels within lung homogenates. The expression of RGMb, p38 MAPK, and Erk1/2 pathways was detected using a fully automated digital Western blotting system WES (ProteinSimple, USA). Flow cytometry was employed to analyze tissue-resident memory T cells (TRM) within the lung. Subsequently, the siRNA gene was employed to induce the downregulation of RGMb in mice in order to validate the involvement of RGMb in radiation-immune lung injury. The present study observed a significant increase in both inflammatory and fibrotic indicators within the mice group's lung tissue that received the combination treatment. The combination group exhibited elevated levels of TGF-I3, TNF-alpha, IL-6, and IL-1I3 in lung homogenates. Anti-PD-1 antibody and carbon ion irradiation, upregulated RGMb, phospho-p38 MAPK and phospho-Erk1/2. The results obtained from the flow cytometry analysis indicated that the combination group was significantly higher in the number of clonal expansion TRMs, which were predominantly characterized by the expression of CD8+CD103+CD69-TRMs. The downregulate of RGMb via siRNA in mice resulted in a decrease in phospho-p38 MAPK and phospho-Erk1/2. The combination group exhibited a reduction in TNF-alpha, TGF-I3, IL-6, and IL-1I3 in their lung tissues, and the number of CD8+CD103+CD69-TRM was significantly reduced. The combination group exhibited a significant improvement in inflammatory and fibrotic indicators within the lung tissues. AntiPD-1 antibody and carbon ion irradiation synergistically regulate RGMb, leading to strong clonal expansion of lung TRM through the p38 MAPK and Erk1/2 pathways. The present study offers valuable insights into the treatment of lung injury due to the combined administration of carbon ion radiotherapy and anti-PD-1 antibody therapy.