title: Estrogen selectively promotes the differentiation of dendritic cells with characteristics of Langerhans cells.
abstract: The steroid hormone estrogen regulates the differentiation, survival, or function of diverse immune cells. Previously, we found that physiological amounts of 17beta-estradiol act via estrogen receptors (ER) to promote the GM-CSF-mediated differentiation of dendritic cells (DC) from murine bone marrow progenitors in ex vivo cultures. Of the two major subsets of CD11c(+) DC that develop in these cultures, estrogen is preferentially required for the differentiation of a CD11b(int)Ly6C(-) population, although it also promotes increased numbers of a CD11b(high)Ly6C(+) population. Although both DC subsets express ERalpha, only the CD11b(high)Ly6C(+) DC express ERbeta, perhaps providing a foundation for the differential regulation of these two DC types by estrogen. The two DC populations exhibit distinct phenotypes in terms of capacity for costimulatory molecule and MHC expression, and Ag internalization, which predict functional differences. The CD11b(int)Ly6C(-) population shows the greatest increase in MHC and CD86 expression after LPS activation. Most notably, the estrogen-dependent CD11b(int)Ly6C(-) DC express langerin (CD207) and contain Birbeck granules characteristic of Langerhans cells. These data show that estrogen promotes a DC population with the unique features of epidermal Langerhans cells and suggest that differentiation of Langerhans cells in vivo will be dependent upon local estrogen levels and ER-mediated signaling events in skin.
authors.affiliation: Division of Immunology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Allen
authors.initials: A
authors.lastname: Mao
authors.forename: Vladislava
authors.initials: V
authors.lastname: Paharkova-Vatchkova
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Marcia M
authors.initials: MM
authors.lastname: Miller
authors.forename: Susan
authors.initials: S
authors.lastname: Kovats
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000096:biosynthesis / Q000502:physiology*; D004967:Estrogens / Q000502:physiology; D005260:Female; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D037241:Mannose-Binding Lectins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D017077:Culture Media, Conditioned; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D012333:RNA, Messenger