Steady state dendritic cells with forced IDO expression induce skin allograft tolerance by upregulation of regulatory T cells.
Despite recent extensive studies, the molecular mechanism through which DCs induce allograft tolerance largely remains poorly understood. In the current study, we presented strong evidence supporting a role for IDO in DC-mediated allograft tolerance. Pre-treatment of recipient mice with IDO-transduced donor-specific BMDCs induced skin allograft tolerance in an antigen-dependent manner. Our data suggest that IDO-expressing DCs may regulate a delicate balance of cytokines that favors the differentiation of naïve CD4+ T cells into Tregs instead of CD4+ effector T cells. In addition, BMDCs with forced IDO expression also have higher capability to expand natural Tregs. In consistent with the observation of augmented Tregs detected in the recipient mice, the capacity for splenic T cell alloresponse was significantly reduced in recipient mice pre-treated with IDO-transduced BMDCs. Furthermore, the expression of inflammatory cytokines such as IL-2, IFNgamma, IL-6, IL-17A and IL-23p19, in splenic T cells of these recipient mice, was significantly lower as compared to that of recipient mice pre-treated with either GFP-transduced BMDCs or untransduced BMDCs.
Yu
Guang
G
Laboratory of Transplantation, Department of Immunology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
Fang
Min
M
Gong
Min
M
Liu
Li
L
Zhong
Jixin
J
Feng
Wei
W
Xiong
Ping
P
Wang
Cong-Yi
CY
Gong
Feili
F
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology*; D015854:Up-Regulation
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase