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Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells

Nature Immunology volume 5, pages 1124–1133 (2004)Cite this article

A Corrigendum to this article was published on 20 October 2014

Abstract

The fates of dendritic cells (DCs) after antigen presentation have been studied extensively, but the influence of lymphoid microenvironments on DCs is mostly unknown. Here, using splenic stromal cells to mimic the immune microenvironment, we show that contact with stromal cells promoted mature DCs to proliferate in a fibronectin-dependent way and that both stromal cell contact and stromal cell–derived transforming growth factor-β induced their differentiation into a new regulatory DC subset. We have identified an in vivo counterpart in the spleen with similar phenotype and functions. These differentiated DCs secreted nitric oxide, which mediated the suppression of T cell proliferation in response to antigen presentation by mature DCs. Thus, our findings identify an important mechanism by which the microenvironment regulates immune responses.

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Figure 1: ESSCs promote maDC proliferation.
Figure 2: Characteristics of ESSC-differentiated DCs.
Figure 3: The diffDCs activate T cells but inhibit their proliferation.
Figure 4: Mechanisms underlying differentiation and function of diffDCs.
Figure 5: Identification of in vivo counterparts of diffDCs.

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Acknowledgements

We thank C. Luo and R. Zhang for technical assistance and acknowledge the comments of J. Rayner and Y.-W. He. Supported by grants from the National Natural Science Foundation of China (30121002, 30000151, 30128022) and the National Key Basic Research Program of China (2001CB510002).

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Author notes

  1. Minghui Zhang, Hua Tang and Zhenhong Guo: These authors contributed equally to this work.

Authors and Affiliations

  1. The Institute of Immunology, Second Military Medical University, Shanghai, China

    Minghui Zhang, Zhenhong Guo, Huazhang An, Xuejun Zhu, Wengang Song, Jun Guo, Xin Huang, Taoyong Chen & Xuetao Cao

  2. The Institute of Immunology, Zhejiang University, Hangzhou, China

    Hua Tang, Jianli Wang & Xuetao Cao

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  1. Minghui Zhang
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Correspondence to Xuetao Cao.

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Supplementary information

Supplementary Fig. 1

Characteristics of mouse ESSCs. ESSCs, cultured from newborn mouse spleen were positively selected based on CD106 expression. (PDF 678 kb)

Supplementary Fig. 2

The morphology of maDCs and diffDCs. (PDF 772 kb)

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Zhang, M., Tang, H., Guo, Z. et al. Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat Immunol 5, 1124–1133 (2004). https://doi.org/10.1038/ni1130

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