Moravej Ali, Geramizadeh Bita, Azarpira Negar, Zarnani Amir-Hassan, Yaghobi Ramin, Kalani Mehdi, Khosravi Maryam, Kouhpayeh Amin, Karimi Mohammad-Hossein
Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran; Noncommunicable Diseases Research Centre, Fasa University of Medical Sciences, Fasa, Iran.
Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
Immunol Lett. 2017 Feb;182:39-49. doi: 10.1016/j.imlet.2017.01.005. Epub 2017 Jan 6.
Recently, mesenchymal stem cells (MSCs) have gained considerable interests as hopeful therapeutic cells in transplantation due to their immunoregulatory functions. But exact mechanisms underlying MSCs immunoregulatory function is not fully understood. Herein, in addition to investigate the ability of MSCs to prolong graft survival time, the effects of them on the expression of PD-L1 and IDO immunomodulatory molecules in splenocytes of skin graft recipient mice was clarified. To achieve this goal, full-thickness skins were transplanted from C57BL/6 to BALB/c mice. MSCs were isolated from bone marrow of BALB/c mice and injected to the recipient mice. Skin graft survival was monitored daily to determine graft rejection time. On days 2, 5 and 10 post skin transplantation, serum cytokine levels and expression of PD-L1 and IDO mRNA and protein in the splenocytes of recipient mice were evaluated. The results showed that administration of MSCs prolonged skin graft survival time from 11 to 14 days. On days 2 and 5 post transplantation, splenocytes PD-L1 expression and IL-10 serum level in MSCs treated mice were higher than those in the controls, while IL-2 and IFN-γ levels were lower. Rejection in MSCs treated mice was accompanied by an increase in IL-2 and IFN-γ, and decrease in PD-L1 expression and IL-10 level. No difference in the expression of IDO between MSCs treated mice and controls was observed. In conclusion, we found that one of the mechanisms underlying MSCs immunomodulatory function could be up-regulating PD-L1 expression.
最近，间充质干细胞（MSCs）因其免疫调节功能而作为移植中有希望的治疗细胞引起了广泛关注。但MSCs免疫调节功能的确切机制尚未完全阐明。在此，除了研究MSCs延长移植物存活时间的能力外，还阐明了它们对皮肤移植受体小鼠脾细胞中PD-L1和IDO免疫调节分子表达的影响。为实现这一目标，将C57BL/6小鼠的全层皮肤移植到BALB/c小鼠身上。从BALB/c小鼠的骨髓中分离出MSCs并注射到受体小鼠体内。每天监测皮肤移植存活情况以确定移植排斥时间。在皮肤移植后的第2、5和10天，评估受体小鼠脾细胞中血清细胞因子水平以及PD-L1和IDO mRNA和蛋白的表达。结果表明，给予MSCs可使皮肤移植存活时间从11天延长至14天。在移植后的第2天和第5天，接受MSCs治疗的小鼠脾细胞中PD-L1表达和血清IL-10水平高于对照组，而IL-2和IFN-γ水平较低。接受MSCs治疗的小鼠发生排斥反应时，IL-2和IFN-γ增加，PD-L1表达和IL-10水平降低。在接受MSCs治疗的小鼠和对照组之间未观察到IDO表达的差异。总之，我们发现MSCs免疫调节功能的潜在机制之一可能是上调PD-L1表达。
