Peking University People's Hospital, Beijing, 100044, China.
Peking University Institute of Hematology, Beijing, 100044, China.
Sci China Life Sci. 2020 Nov;63(11):1744-1754. doi: 10.1007/s11427-019-1691-x. Epub 2020 May 6.
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 F4/80iNOS 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 F4/80CD206 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 F4/80iNOS cells, and increased the number of F4/80CD206 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.
本研究旨在探讨造血干细胞移植后急性移植物抗宿主病（GVHD）中的巨噬细胞极化，并研究三氧化二砷（ATO）是否可以纠正这种失衡。在 GVHD 小鼠的结肠中，我们发现 F4/80iNOS 细胞的数量以及 TNF-α 和 IL-1β 的表达强度在 GVHD 组中比 BM 组更高，而 F4/80CD206 细胞的数量以及 IL-10 和 TGF-β 的表达强度在 BM 组中比 GVHD 组更高。我们研究了 ATO 对 GVHD 小鼠的影响，发现 ATO 治疗明显改善了小鼠的存活率并减轻了 GVHD 的严重程度。此外，ATO 减少了 GVHD 小鼠结肠中 F4/80iNOS 细胞的数量，并增加了 F4/80CD206 细胞的数量。此外，ATO 明显降低了从 aGVHD 患者诱导的巨噬细胞中 CD86 和 CD80 的表达，并增加了 CD163 和 CD206 的表达。因此，ATO 可以调节 GVHD 小鼠或 aGVHD 患者巨噬细胞中的 M1 和 M2 表型。我们的数据表明，巨噬细胞极化参与了 aGVHD 的发病机制，而 ATO 治疗可调节巨噬细胞向 M2 表型极化。
