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Article
Nature Immunology  5, 1124 - 1133 (2004)
Published online: 10 October 2004; | doi:10.1038/ni1130

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

Minghui Zhang1, 3, Hua Tang2, 3, Zhenhong Guo1, 3, Huazhang An1, Xuejun Zhu1, Wengang Song1, Jun Guo1, Xin Huang1, Taoyong Chen1, Jianli Wang2 & Xuetao Cao1, 2

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

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

3  These authors contributed equally to this work.

Correspondence should be addressed to Xuetao Cao caoxt@public3.sta.net.cn
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-beta 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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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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