title: Indoleamine 2,3-dioxygenase and regulatory dendritic cells contribute to the allograft protection induced by infusion of donor-specific splenic stromal cells.
abstract: 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.
authors.affiliation: Laboratory of Transplantation, Department of Immunology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Lihua
authors.initials: L
authors.lastname: Duan
authors.forename: Min
authors.initials: M
authors.lastname: Gong
authors.forename: Hong
authors.initials: H
authors.lastname: Dai
authors.forename: Quan
authors.initials: Q
authors.lastname: Gong
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
authors.forename: Congyi
authors.initials: C
authors.lastname: Wang
authors.forename: Feili
authors.initials: F
authors.lastname: Gong
authors.forename: Min
authors.initials: M
authors.lastname: Fang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016753:Interleukin-10