title: 17beta-estradiol alters the activity of conventional and IFN-producing killer dendritic cells.
abstract: Estrogens increase aspects of innate immunity and contribute to sex differences in the prevalence of autoimmune diseases and in response to infection. The goal of the present study was to assess whether exposure to 17beta-estradiol (E2) affects the development and function of bone marrow-derived dendritic cells and to determine whether similar changes are observed in CD11c(+) splenocytes exposed to E2 in vivo. E2 facilitated the differentiation of BM precursor cells into functional CD11c(+)CD11b(+)MHC class II(+) dendritic cells (DCs) with increased expression of the costimulatory molecules CD40 and CD86. Exposure of bone marrow-derived dendritic cells to E2 also enhanced production of IL-12 in response to the TLR ligands, CpG and LPS. In contrast, CD11c(+) cells isolated from the spleens of female C57BL/6 mice that were intact, ovariectomized, or ovariectomized with E2 replacement exhibited no differences in the number or activity of CD11c(+)CD11b(+)MHC class II(+) DCs. The presence of E2 in vivo, however, increased the number of CD11c(+)CD49b(+)NK1.1(low) cells and reduced numbers of CD11c(+)CD49b(+)NK1.1(high) cells, a surface phenotype for IFN-producing killer DCs (IKDCs). Ultrastructural analysis demonstrated that CD11c(+)NK1.1(+) populations were comprised of cells that had the appearance of both DCs and IKDCs. CD11c(+) splenocytes isolated from animals with supplemental E2 produced more IFN-gamma in response to IL-12 and IL-18. These data illustrate that E2 has differential effects on the development and function of DCs and IKDCs and provide evidence that E2 may strengthen innate immunity by enhancing IFN-gamma production by CD11c(+) cells.
authors.affiliation: The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Siracusa
authors.forename: Michael G
authors.initials: MG
authors.lastname: Overstreet
authors.forename: Franck
authors.initials: F
authors.lastname: Housseau
authors.forename: Alan L
authors.initials: AL
authors.lastname: Scott
authors.forename: Sabra L
authors.initials: SL
authors.lastname: Klein
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D039521:CD11c Antigen / Q000032:analysis; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D018960:Hyaluronan Receptors / Q000032:analysis; D007113:Immunity, Innate / Q000187:drug effects; D039421:Integrin alpha2 / Q000032:analysis; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D012737:Sex Factors; D013154:Spleen / Q000187:drug effects / Q000276:immunology
chemical_list: D051940:B7-2 Antigen; D039521:CD11c Antigen; D047628:Estrogen Receptor alpha; D004967:Estrogens; D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; D039421:Integrin alpha2; D004958:Estradiol; D007371:Interferon-gamma