Indoleamine 2,3-dioxygenase and regulatory dendritic cells contribute to the allograft protection induced by infusion of donor-specific splenic stromal cells

作     者：Li Liu Lihua Duan Min Gong Hong Dai Quan Gong Fang Zheng Zheng Tan Congyi Wang Feili Gong Min Fang 

作者机构：Laboratory of TransplantationDepartment of ImmunologyTongji Medical College of Huazhong University of Science and TechnologyWuhanChina The Center for Biomedical ResearchTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2011年第8卷第1期

页      面：31-40页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：This work was supported by the National Natural Science Foundation of China(grants 30772039 and 81072440) the National Natural Science Foundation of China-Guangdong Province Union Grant(U0832003) the Ministry of Science and Technology of China(grant 2007CB512402) 

主　　题：dendritic cell indoleamine 2,3-dioxygenase splenic stromal cell transplantation 

摘      要：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 *** 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 ***,the precise mechanisms by which these SSCs exert their regulatory functions in vivo remain ***,their possible contribution to the development of allograft transplantation tolerance has yet to be ***,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 *** show that intravenous SSC infusion prolonged murine skin allograft *** 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)-***,we found that indoleamine 2,3-dioxygenase and SSC-derived regulatory DCs contribute to allograft protection by infusion of donor-specific *** data suggest that donor-derived SSCs could be used as a therapeutic target to promote transplantation tolerance.