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A R T I C L E S
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l Splenic stroma drives mature dendritic cells to
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m differentiate into regulatory dendritic cells
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t 1,3 2,3 1,3 1 1 1 1
a Minghui Zhang , Hua Tang , Zhenhong Guo , Huazhang An , Xuejun Zhu , Wengang Song , Jun Guo ,
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o Xin Huang , Taoyong Chen , Jianli Wang Xuetao Cao
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t The fates of dendritic cells (DCs) after antigen presentation have been studied extensively, but the influence of lymphoid
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n. microenvironments on DCs is mostly unknown. Here, using splenic stromal cells to mimic the immune microenvironment, we
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w show that contact with stromal cells promoted mature DCs to proliferate in a fibronectin-dependent way and that both stromal
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/ cell contact and stromal cell–derived transforming growth factor-b induced their differentiation into a new regulatory DC subset.
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p We have identified an in vivo counterpart in the spleen with similar phenotype and functions. These differentiated DCs secreted
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nitric oxide, which mediated the suppression of T cell proliferation in response to antigen presentation by mature DCs. Thus, our
p findings identify an important mechanism by which the microenvironment regulates immune responses.
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n Dendritic cells (DCs) are specialized antigen-presenting cells that are on cell-cell contact and transforming growth factor-b (TGF-b). Com-
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h pivotal in immune responses. The different DC subsets and their pared with fully matured DCs, these differentiated DCs (diffDCs) had
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l respective fates have been examined extensively1–5. DCs are commonly lower expression of major histocompatibility compl
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