title: 17 Beta-estradiol (E2) plus tumor necrosis factor-alpha induces a distorted maturation of human monocyte-derived dendritic cells and promotes their capacity to initiate T-helper 2 responses.
abstract: There is growing evidence that 17 beta-estradiol (E2) modulates immune function. Recent studies indicated that certain effects of E2 on in vivo immune function are not a result of a direct action on T cells, but rather an indirect action on antigen-presenting cells. This study demonstrates that the pregnancy-associated doses of E2 plus tumor necrosis factor-alpha (TauNuF alpha) induce distorted maturation of human dendritic cells (DCs) that result in an increased capacity to induce T helper (Th) 2 responses. E2 did not affect the expression of human leukocyte antigen class II and costimulatory molecules by DCs, but elicited the ability of DC to produce CC chemokine ligand 1, which can attract CCR8-expressing Th2 cells and regulatory T cells. In addition, E2/TNF alpha-matured DCs increased the production of IL-10 relative to the IL-12p70 on CD40 ligation, thereby inducing naive T-cell differentiation into a Th2. Moreover, the increased concentration of E2 in the route of maturation did indeed further enhance Th2 deviation. The dominant Th2 deviation was induced at a high E2 concentration typical during pregnancy. These findings demonstrate that the high physiological levels of E2 may be an important endogenous component for regulating the DC function and skewing the immune response toward Th2.
authors.affiliation: Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan. uemura@saitama-med.ac.jp <uemura@saitama-med.ac.jp>
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Uemura
authors.forename: Tian-Yi
authors.initials: TY
authors.lastname: Liu
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Narita
authors.forename: Motoharu
authors.initials: M
authors.lastname: Suzuki
authors.forename: Sho
authors.initials: S
authors.lastname: Matsushita
mesh_terms: D023201:CD40 Ligand / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D054402:Chemokine CCL1 / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008857:Microscopy, Interference; D009000:Monocytes / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D054402:Chemokine CCL1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12; D004958:Estradiol