Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
Division of Hematology and Oncology, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan.
Biol Blood Marrow Transplant. 2017 Oct;23(10):1622-1630. doi: 10.1016/j.bbmt.2017.06.018. Epub 2017 Jul 8.
Professional antigen-presenting cells (APCs) are important modulators of acute graft-versus-host disease (GVHD). Although dendritic cells (DCs) are the most potent APC subset, other myeloid cells, especially macrophages (MFs) and neutrophils, recently have been shown to play a role in the severity of GVHD. The critical molecular mechanisms that determine the functions of myeloid cells in GVHD are unclear, however. Signal transducer and activator of transcription 3 (STAT3) is a master transcription factor that plays a crucial role in regulating immunity, but its role in MF biology and in acute GVHD remains unknown. To determine the impact of myeloid cell-specific expression of STAT3 on the severity of acute GVHD, we used myeloid cell-specific STAT3-deficient LysM-Cre/STAT3 animals as recipients and donors in well-characterized experimental models of acute GVHD. We found that reduced expression of STAT3 in myeloid cells from the hosts, but not the donors, increased inflammation, increased donor T cell activation, and exacerbated GVHD. Our data demonstrate that STAT3 in host myeloid cells, such as MFs, dampens acute GVHD.
专业抗原呈递细胞（APCs）是急性移植物抗宿主病（GVHD）的重要调节剂。虽然树突状细胞（DCs）是最有效的 APC 亚群，但其他髓样细胞，尤其是巨噬细胞（MFs）和中性粒细胞，最近也被证明在 GVHD 的严重程度中发挥作用。然而，决定髓样细胞在 GVHD 中功能的关键分子机制尚不清楚。信号转导子和转录激活子 3（STAT3）是一种重要的转录因子，在调节免疫中起着至关重要的作用，但它在 MF 生物学和急性 GVHD 中的作用尚不清楚。为了确定髓样细胞特异性表达 STAT3 对急性 GVHD 严重程度的影响，我们使用髓样细胞特异性 STAT3 缺陷 LysM-Cre/STAT3 动物作为受体和供体，在急性 GVHD 的典型实验模型中进行了研究。我们发现，宿主而不是供体的髓样细胞中 STAT3 表达减少会增加炎症、增加供体 T 细胞的激活，并加重 GVHD。我们的数据表明，宿主髓样细胞（如 MF）中的 STAT3 可抑制急性 GVHD。
