Splenic stromal microenvironment negatively regulates virus-activated plasmacytoid dendritic cells through TGF-beta.
Plasmacytoid dendritic cells (pDCs) secrete large amounts of IFN-alpha 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 factor 1 (SDF-1), inhibit the secretion of IFN-alpha, IL-12, TNF-alpha, and expression of I-Ab, CD86, CD80, and CD40 by VSV-activated pDCs, and subsequently inhibit VSV-infected pDCs to activate NK cell IFN-gamma production and cytotoxicity. Stroma-derived TGF-beta participates in the negative regulation of VSV-activated pDCs. Therefore, we demonstrate that splenic stromal microenvironment negatively regulates the virus-activated pDCs through TGF-beta, outlining an additional mechanistic explanation for maintenance of immune homeostasis.
Li
Li
L
Institute of Immunology and National Key Laboratory of Medical Immunology, Department of Microbiology, Second Military Medical University, Shanghai, China.
Liu
Shuxun
S
Zhang
Ting
T
Pan
Wei
W
Yang
Xiao
X
Cao
Xuetao
X
D000818:Animals; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006706:Homeostasis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014775:Virus Activation / Q000276:immunology*
D016212:Transforming Growth Factor beta