Arsenic trioxide alleviates acute graft-versus-host disease by modulating macrophage polarization

作     者：Xiao Liu Yan Su Xueyan Sun Haixia Fu Qiusha Huang Qi Chen Xiaodong Mo Meng Lv Yuan Kong Lanping Xu Xiaojun Huang Xiaohui Zhang Xiao Liu;Yan Su;Xueyan Sun;Haixia Fu;Qiusha Huang;Qi Chen;Xiaodong Mo;Meng Lv;Yuan Kong;Lanping Xu;Xiaojun Huang;Xiaohui Zhang

作者机构：Peking University People’s HospitalBeijing 100044China Peking University Institute of HematologyBeijing 100044China National Clinical Research Center for Hematologic DiseaseBeijing 100044China Beijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2020年第63卷第11期

页      面：1744-1754页

核心收录：

学科分类：0710[理学-生物学] 0830[工学-环境科学与工程（可授工学、理学、农学学位）] 1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：supported by the National Key Research and Development Program of China (2017YFA0105500 and 2017YFA0105503) the Beijing Natural Science Foundation (H2018206423) the Key Program of the National Natural Science Foundation of China (81730004) the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621001) the National Natural Science Foundation of China (81670116) the Beijing Natural Science Foundation (7171013) he Beijing Municipal Science and Technology Commission (Z171100001017084) 

主　　题：ATO macrophage polarization acute graft-versus-host disease 

摘      要：This study aimed to explore macrophage polarization in acute graft-versus-host disease after hematopoietic stem cell transplantation, and investigated if arsenic trioxide(ATO) could correct this imbalance. In the colon of GVHD mice, we found that the number of F4/80+iNOS+ cells as well as the expression intensity of TNF-α and IL-1β was greater in the GVHD group than in the BM group, whereas the number of F4/80+CD206+ cells and the expression intensity of IL-10 and TGF-β was greater in the BM group than in the GVHD group. We investigated the effect of ATO on GVHD mice, and found that ATO treatment clearly improved the survival of the mice and reduced the severity of GVHD. In addition, ATO reduced the number of F4/80+iNOS+ cells, and increased the number of F4/80+CD206+ cells in the colon of GVHD mice. Furthermore, ATO sharply decreased CD86 and CD80 expression, and increased CD163 and CD206 expression in macrophages induced from aGVHD patients. Therefore,ATO can modulate the M1 and M2 phenotype in GVHD mice or in macrophages from aGVHD patients. Our data suggest that macrophage polarization is involved in the pathogenesis of aGVHD, and ATO treatment modulates macrophage polarization toward an M2 phenotype.