title: Betamethasone, but Not Tacrolimus, Suppresses the Development of Th2 Cells Mediated by Langerhans Cell-Like Dendritic Cells.
abstract: It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of the immune milieu towards a T helper type 1 (Th1) or T helper type 2 (Th2) response. In this study, we investigated the effects of tacrolimus and betamethasone, each used as topical applications in atopic dermatitis (AD), on Th2 cell development mediated by LCs. LC-like dendritic cells (LDCs) were generated from mouse bone marrow cells and used as substitutes for LCs. Mice were primed with ovalbumin (OVA) peptide-pulsed LDCs, which had been treated with tacrolimus or betamethasone, via the hind footpad. After 5 d, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LDCs was investigated via reverse transcriptase polymerase chain reaction. Administration of OVA peptide-pulsed LDCs, which had been treated with betamethasone, inhibited Th2 cell development, as represented by the down-regulation of interleukin-4 production, and also inhibited Th1 cell development, represented by the down-regulation of interferon-γ production. However, tacrolimus-treated LDCs did not induce such inhibition of the development of Th1 and Th2 cells. The inhibition of Th1 and Th2 cell development was associated with the suppression of CD40 and T-cell immunoglobulin, and mucin domain-containing protein (TIM)-4 expression, respectively, in LDCs. These results suggest that the topical application of betamethasone to skin lesions of patients with AD acts on epidermal LCs, and may inhibit the development of Th2 cells, thus being of benefit for the control of AD.
authors.affiliation: Department of Microbial Science and Host Defense, Meiji Pharmaceutical University.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Matsui
authors.forename: Saki
authors.initials: S
authors.lastname: Tamai
authors.forename: Reiko
authors.initials: R
authors.lastname: Ikeda
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001623:Betamethasone / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016559:Tacrolimus / Q000494:pharmacology*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D000485:Allergens; D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin; D001623:Betamethasone; D016559:Tacrolimus