title: Dexamethasone preferentially suppresses plasmacytoid dendritic cell differentiation and enhances their apoptotic death.
abstract: Plasmacytoid dendritic cells (pDC) are an important source of type-1 interferon (IFN) following microbial infection and also play key roles in the induction of innate and adaptive immune responses. Here, we show that the glucocorticoid (GC) dexamethasone (Dex) strikingly reduces pDC (and myeloid DC) numbers in secondary lymphoid tissue and liver of normal and hematopoietic growth factor-mobilized mice and suppresses pDC differentiation from bone marrow precursors in vitro. Moreover, the apoptotic death of pDC in vitro was enhanced by exposure to Dex. Notably, however, Toll-like receptor 9 expression and virally induced IFNalpha production by residual pDC from Dex-treated animals were unaffected. Thus, whereas marked reduction in absolute numbers of pDC by GC may predispose to viral infection, often associated with GC-mediated immunosuppression, reductions in pDC and IFNalpha production may contribute to the beneficial effects on GC observed in systemic autoimmune disease, in which that both pDC and IFNalpha have been implicated.
authors.affiliation: Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, E1504 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213, USA. abem@upmc.edu
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
authors.forename: Angus W
authors.initials: AW
authors.lastname: Thomson
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D003907:Dexamethasone