Indoleamine 2,3-dioxygenase and regulatory dendritic cells contribute to the allograft protection induced by infusion of donor-specific splenic stromal cells
Indoleamine 2,3-dioxygenase and regulatory dendritic cells contribute to the allograft protection induced by infusion of donor-specific splenic stromal cells
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吲哚胺2,3-双加氧酶和调节性树突状细胞有助于输注供体特异性脾基质细胞诱导的同种异体移植物保护
DOI：
10.1038/cmi.2010.53
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Gong, Feili
中科院分区：
文献类型：
--
作者：
Fang, Min;Duan, Lihua;Gong, Min;Dai, Hong;Gong, Quan;Zheng, Fang;Tan, Zheng;Wang, Congyi;Gong, Feili
据报道，脾基质细胞（SSCs）能够在不存在外源性细胞因子的情况下直接支持谱系阴性c-kit（+）祖细胞向产生CD 11 c（lo）CD 45 RB（+）IL-10的树突状细胞（DC）的发育。在体外，在基质细胞上分化的DC抑制混合白细胞反应，并诱导初级同种异体反应性CD 4（+）T细胞分化为产生IL-10的Tr 1细胞。然而，这些精原干细胞在体内发挥其调节功能的确切机制仍不清楚。此外，它们对同种异体移植耐受性发展的可能贡献还有待研究。在这里，我们使用小鼠皮肤和心脏同种异体移植模型，以探讨是否在体内同种异体反应可以通过输注供体来源的SSC进行调节，并探讨SSC发挥调节作用，以防止同种异体移植排斥反应的可能机制。我们发现静脉内SSC输注延长了小鼠皮肤移植物的存活。延长的移植物存活与调节性DC亚群和CD 4（+）CD 25（+）Foxp 3（+）调节性T细胞（TcB）的产生增加以及抑制性细胞因子IL-10和转化生长因子（TGF）-β的产生上调有关。此外，我们发现吲哚胺2，3-双加氧酶和SSC衍生的调节性DC通过输注供体特异性SSC有助于同种异体移植物保护。我们的数据表明，供体来源的精原干细胞可以作为一个治疗靶点，以促进移植耐受。
It has been reported that splenic stromal cells (SSCs) are capable of directly supporting the development of CD11c(lo)CD45RB(+ )IL-10-producing dendritic cells (DCs) from lineage-negative c-kit(+) progenitor cells in the absence of exogenous cytokines. In vitro, DCs that differentiate on stromal cells suppress mixed leukocyte reaction responses and induce primary alloreactive CD4(+) T cells to differentiate into IL-10-producing Tr1 cells. However, the precise mechanisms by which these SSCs exert their regulatory functions in vivo remain undefined. Furthermore, their possible contribution to the development of allograft transplantation tolerance has yet to be examined. Here, we have used both murine skin and cardiac allograft transplantation models to explore whether in vivo alloresponses can be regulated by infusion with donor-derived SSCs and to investigate the possible mechanisms by which SSCs exert regulatory effects to prevent allograft rejection. We show that intravenous SSC infusion prolonged murine skin allograft survival. The prolonged graft survival is associated with augmentation of the generation of regulatory DC subsets and CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), as well as upregulation of the production of suppressive cytokines IL-10 and transforming growth factor (TGF)-β. Moreover, we found that indoleamine 2,3-dioxygenase and SSC-derived regulatory DCs contribute to allograft protection by infusion of donor-specific SSCs. Our data suggest that donor-derived SSCs could be used as a therapeutic target to promote transplantation tolerance.
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影响因子：
32.4
作者：
Svensson, M;Maroof, A;Kaye, PM
通讯作者：
Kaye, PM
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
4.4
作者：
Haniffa, Muzlifah A.;Wang, Xiao-Nong;Collin, Matthew P.
通讯作者：
Collin, Matthew P.
影响因子：
20.3
作者：
Meisel, R;Zibert, A;Dilloo, D
通讯作者：
Dilloo, D
CD8α(+)树突状细胞负责诱导外周组织相关抗原的自身耐受。
影响因子：
15.3
作者：
Belz, Gabrielle T;Behrens, Georg M N;Smith, Chris M;Miller, Jacques F A P;Jones, Claerwen;Lejon, Kristina;Fathman, C Garrison;Mueller, Scott N;Shortman, Ken;Carbone, Francis R;Heath, William R
通讯作者：
Heath, William R