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

Cellular & Molecular Immunology volume 8, pages 31–40 (2011)Cite this article

An Erratum to this article was published on 04 January 2011

This article has been updated

Abstract

It has been reported that splenic stromal cells (SSCs) are capable of directly supporting the development of CD11cloCD45RB+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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  • 04 January 2011

    This article has been corrected since Advance Online Publication and an erratum is also printed in this issue

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Acknowledgements

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) and the Ministry of Science and Technology of China (grant 2007CB512402). We thank Ping Xiong and Yong Xu for technical assistance.

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Author notes

  1. Li Liu and Lihua Duan: These authors contributed equally to this study.

  2. Dr M Fang, Department of Immunology, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan 430030, China. E-mail: minfang89@mail.hust.edu.cn

Authors and Affiliations

  1. Department of Immunology, Laboratory of Transplantation, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China

    Li Liu, Lihua Duan, Min Gong, Hong Dai, Quan Gong, Fang Zheng, Zheng Tan, Feili Gong & Min Fang

  2. The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Congyi Wang

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This article has been corrected since Advance Online Publication and an erratum is also printed in this issue

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Liu, L., Duan, L., Gong, M. et al. Indoleamine 2,3-dioxygenase and regulatory dendritic cells contribute to the allograft protection induced by infusion of donor-specific splenic stromal cells. Cell Mol Immunol 8, 31–40 (2011). https://doi.org/10.1038/cmi.2010.53

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