Arsenic trioxide alleviates acute graft-versus-host disease by modulating macrophage polarization
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senic trioxide alleviates acute graft-versus-host disease by modulating macrophage polarization 1,2,3,4†
1,2,3,4†
1,2,3,4
1,2,3,4
1,2,3,4
1,2,3,4
Xiao Liu , Yan Su , Xueyan Sun , Haixia Fu , Qiusha Huang , Qi Chen , 1,2,3,4 1,2,3,4 1,2,3,4 1,2,3,4 1,2,3,4 , Meng Lv , Yuan Kong , Lanping Xu , Xiaojun Huang & Xiaodong Mo 1,2,3,4* Xiaohui Zhang 1
Peking University People’s Hospital, Beijing 100044, China; Peking University Institute of Hematology, Beijing 100044, China; 3 National Clinical Research Center for Hematologic Disease, Beijing 100044, China; 4 Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China 2
Received December 26, 2019; accepted March 27, 2020; published online May 6, 2020
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. ATO, macrophage polarization, acute graft-versus-host disease Citation:
Liu, X., Su, Y., Sun, X., Fu, H., Huang, Q., Chen, Q., Mo, X., Lv, M., Kong, Y., Xu, L., et al. (2020). Arsenic trioxide alleviates acute graft-versus-host disease by modulating macrophage polarization. Sci China Life Sci 63, https://doi.org/10.1007/s11427-019-1691-x
INTROUDUCTION Acute graft-versus-host disease (aGVHD) is a prominent complication with an incidence of 10%–80% after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and can be one of the leading causes of death in these patients (Dignan et al., 2012). Despite momentous advances in the understanding of the pathogenesis, prophylaxis, and treatment of aGVHD in recent years, over 50% of patients are †Contributed equally to this work *Corresponding author (email: [email protected])
refractory to standard corticosteroid intervention (Zeiser et al., 2016). Therefore, it is urgent to uncover important factors involved in aGVHD pathogenesis and explore effective treatments. aGVHD is an intricate disease that is triggered by the imm
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