Gong Weihua, Shou Dawei, Cheng Fei, Shi Jianguang, Ge Fangmin, Liu Dahai
Department of Surgery and Medicine, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou City, People's Republic of China; Department of Medicine, Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Department of Surgery and Medicine, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou City, People's Republic of China.
Transpl Immunol. 2015 Mar;32(2):72-5. doi: 10.1016/j.trim.2015.02.001. Epub 2015 Feb 10.
Transplant tolerance induced by IL-6 deficient donor is supported by regulatory T cells (Tregs). However, it is unknown whether innate immunoregulatory cells such as myeloid-derived suppressor cells (MDSCs) are involved in the process.
In this study, we demonstrate the role of MDSCs by transplanting IL-6 deficient heart grafts into wild-type recipients in a murine allogeneic transplant model.
Our data further revealed that utilization of IL-6 deficient heart grafts could cause a significant prolongation of allograft survival (Mantel-Cox Test, p = 0.001; Gehan-Breslow-Wilcoxon Test, p = 0.0016) and a remarkable increase of the frequency of CD11b + Gr1(-low) in the recipients' spleens (p = 0.0028).
MDSCs rather than Th17 cells are closely involved in induced tolerance by IL-6 deficient donor heart. This unveiled mechanism of targeting IL-6 or its signaling pathway may provide a novel insight into preventing allograft rejection for non-sensitized transplant recipients.
白细胞介素-6（IL-6）缺陷供体诱导的移植耐受由调节性T细胞（Tregs）支持。然而，尚不清楚诸如髓源性抑制细胞（MDSCs）等先天性免疫调节细胞是否参与该过程。
在本研究中，我们通过将IL-6缺陷心脏移植物移植到小鼠同种异体移植模型中的野生型受体中来证明MDSCs的作用。
我们的数据进一步显示，使用IL-6缺陷心脏移植物可导致同种异体移植物存活时间显著延长（Mantel-Cox检验，p = 0.001；Gehan-Breslow-Wilcoxon检验，p = 0.0016），并且受体脾脏中CD11b + Gr1（-低）频率显著增加（p = 0.0028）。
MDSCs而非Th17细胞密切参与IL-6缺陷供体心脏诱导的耐受。这种针对IL-6或其信号通路的揭示机制可能为预防未致敏移植受者的同种异体移植物排斥提供新的见解。
