Combining Exosomes Derived from Immature DCs with Donor Antigen-Specific Treg Cells Induces Tolerance in a Rat Liver Allograft Model.
Combining Exosomes Derived from Immature DCs with Donor Antigen-Specific Treg Cells Induces Tolerance in a Rat Liver Allograft Model.
复制标题
将未成熟 DC 衍生的外泌体与供体抗原特异性 Treg 细胞相结合可在大鼠肝脏同种异体移植模型中诱导耐受性
DOI：
10.1038/srep32971
复制
发表时间：
2016-09-19
影响因子：
4.6
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Ma B;Yang JY;Song WJ;Ding R;Zhang ZC;Ji HC;Zhang X;Wang JL;Yang XS;Tao KS;Dou KF;Li X
同种异体移植耐受是移植免疫学研究的最终目标。未成熟树突状细胞（imDCs）在建立免疫耐受中起着重要作用，但也有其局限性，包括成熟潜力、体内寿命短和体外储存时间短。然而，来自imDC（imDex）的外来体（通常为30-100 nm）保留了许多源细胞特性，并且可以克服这些限制。在以前的报道中，imDex延长了心脏或肠移植物的存活时间。然而，除非使用免疫抑制剂，否则无法实现耐受或长期生存。调节性T细胞（Regulatory T cells，Tcells）可以保护同种异体移植物免受免疫排斥反应，我们以前的研究表明imDex的作用与Tcells显著相关。因此，我们在治疗方案中纳入了TdR，以进一步减少或避免抑制剂的使用。我们将大鼠肝移植中的最佳外泌体剂量定义为约20 μg（移植前、移植期间和移植后每次治疗），并确定了TGFAP在保护肝移植物中的抗原特异性作用。在联合治疗组中，受体获得长期存活，并诱导耐受。此外，imDex扩增TcR，其需要受体DC并通过IL-2增强。幸运的是，扩增的TdR保留了它们的调节能力和供体特异性。因此，imDex和供体特异性Tcl 3可以协同诱导移植物耐受。
Allograft tolerance is the ultimate goal in the field of transplantation immunology. Immature dendritic cells (imDCs) play an important role in establishing tolerance but have limitations, including potential for maturation, short lifespanin vivoand short storage timesin vitro. However, exosomes (generally 30–100 nm) from imDCs (imDex) retain many source cell properties and may overcome these limitations. In previous reports, imDex prolonged the survival time of heart or intestine allografts. However, tolerance or long-term survival was not achieved unless immune suppressants were used. Regulatory T cells (Tregs) can protect allografts from immune rejection, and our previous study showed that the effects of imDex were significantly associated with Tregs. Therefore, we incorporated Tregs into the treatment protocol to further reduce or avoid suppressant use. We defined the optimal exosome dose as approximately 20 μg (per treatment before, during and after transplantation) in rat liver transplantation and the antigen-specific role of Tregs in protecting liver allografts. In the co-treatment group, recipients achieved long-term survival, and tolerance was induced. Moreover, imDex amplified Tregs, which required recipient DCs and were enhanced by IL-2. Fortunately, the expanded Tregs retained their regulatory ability and donor-specificity. Thus, imDex and donor-specific Tregs can collaboratively induce graft tolerance.
登录
查看更多内容
DOI：
10.1073/pnas.1303906110
发表时间：
2013-07-30
影响因子：
11.1
作者：
Meckes, David G., Jr.;Gunawardena, Harsha P.;Raab-Traub, Nancy
通讯作者：
Raab-Traub, Nancy
影响因子：
30.5
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
25.7
作者：
Nojima H;Freeman CM;Schuster RM;Japtok L;Kleuser B;Edwards MJ;Gulbins E;Lentsch AB
通讯作者：
Lentsch AB
影响因子：
6.4
作者：
Kang, Hee Gyung;Lee, Jung Eun;Kim, Yon Su
通讯作者：
Kim, Yon Su
影响因子：
8.8
作者：
Siepert, A.;Ahrlich, S.;Reinke, P.
通讯作者：
Reinke, P.