Nakao T, Nakamura T, Masuda K, Matsuyama T, Ushigome H, Ashihara E, Yoshimura N
Department of Organ Transplantation and Regenerative Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Organ Transplantation and Regenerative Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Transplant Proc. 2018 Jan-Feb;50(1):299-304. doi: 10.1016/j.transproceed.2017.11.014.
Recently, myeloid-derived suppressor cells (MDSCs) have attracted considerable attention because of their cancer-promoting and immunosuppressive effects. The glucocorticoid dexamethasone (Dex) is an important immunosuppressive agent used to treat autoimmune diseases and organ transplant rejection. However, the mechanism by which it modulates the immune system is not completely understood.
In this study, we investigated the mechanisms by which Dex modulated the immune response in mice given an allogeneic cardiac transplant.
Dex injection significantly prolonged heart graft survival compared with phosphate-buffered saline-injected controls. Dex treatment increased the number of splenic MDSCs. Moreover, Gr-1/CD11b MDSCs and CD3/CD4/Foxp3 regulatory T cells (Tregs) were significantly increased in the Dex group compared with controls. Administration of anti-Gr-1 antibody (Ab) to the Dex group significantly shortened mouse heart graft survival. In addition, anti-Gr-1 Ab treatment significantly reduced Tregs in the Dex + anti-Gr-1 co-treatment group compared with the Dex group. These observations suggest that Dex treatment increased both MDSCs and Tregs, and that MDSCs regulated the incidence of Tregs in this immunosuppressive pathway.
An important role of Dex in the prevention of the rejection of cardiac grafts in mice is to expand MDSCs and Tregs.
最近，髓源性抑制细胞（MDSCs）因其促进癌症和免疫抑制作用而备受关注。糖皮质激素地塞米松（Dex）是一种用于治疗自身免疫性疾病和器官移植排斥反应的重要免疫抑制剂。然而，其调节免疫系统的机制尚未完全明确。
在本研究中，我们探究了地塞米松调节同种异体心脏移植小鼠免疫反应的机制。
与注射磷酸盐缓冲盐水的对照组相比，注射地塞米松显著延长了心脏移植的存活时间。地塞米松治疗增加了脾脏MDSCs的数量。此外，与对照组相比，地塞米松组中Gr-1/CD11b MDSCs和CD3/CD4/Foxp3调节性T细胞（Tregs）显著增加。向地塞米松组注射抗Gr-1抗体（Ab）显著缩短了小鼠心脏移植的存活时间。此外，与地塞米松组相比，抗Gr-1 Ab治疗在Dex +抗Gr-1联合治疗组中显著降低了Tregs。这些观察结果表明，地塞米松治疗增加了MDSCs和Tregs，并且MDSCs在这种免疫抑制途径中调节了Tregs的发生率。
地塞米松在预防小鼠心脏移植排斥反应中的一个重要作用是扩增MDSCs和Tregs。
