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* Institute of Immunology and National Key Laboratory of Medical Immunology and
Department of Microbiology, Second Military Medical University, Shanghai, China;
Institute of Immunology, Zhejiang University, Hangzhou, China; and
Beijing Institute of Biotechnology, Beijing, China
Plasmacytoid dendritic cells (pDCs) secrete large amounts of IFN-
upon exposure to virus, subsequently promoting and regulating innate and adaptive immune responses. However, little is known about the functional regulation of virus-activated pDCs after they exert functions in secondary lymph organs. Our previous studies show that splenic stromal microenvironment can down-regulate the T cell response by inducing generation of regulatory myeloid dendritic cells; therefore, we wondered whether the splenic stromal microenvironment can regulate the function of virus-activated pDCs. In this study, we provide evidences that the splenic stromal microenvironment can chemoattract vesicular stomatitis virus (VSV)-activated pDCs via stromal cell-derived dactor 1 (SDF-1), inhibit the secretion of IFN-, IL-12, TNF-, and expression of I-Ab, CD86, CD80, and CD40 by VSV-activated pDCs, and subsequently inhibit VSV-infected pDCs to activate NK cell IFN-
production and cytotoxicity. Stroma-derived TGF-β participates in the negative regulation of VSV-activated pDCs. Therefore, we demonstrate that splenic stromal microenvironment negatively regulates the virus-activated pDCs through TGF-β, outlining an additional mechanistic explanation for maintenance of immune homeostasis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the National Natural Science Foundation of China (30490240, 30121002, 30471573), National Key Basic Research Program of China (2007CB512403), and Shanghai Committee of Science and Technology (05DZ22106).
2 L.L. and S.L. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Xuetao Cao, Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. E-mail address: caoxt{at}public3.sta.net.cn
4 Abbreviations used in this paper: pDC, plasmacytoid dendritic cell; DC, dendritic cell; ESSC, endothelial splenic stromal cell; VSV, vesicular stomatitis virus; SDF-1, stromal cell-derived factor 1; Flt-3L, FMS-like tyrosine kinase 3 ligand; 7-AAD, 7-aminactinomycin D; ESSC-SN, ESSC-derived supernatant; Treg, regulatory T cell.
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