Aberrant function of peripheral blood myeloid and plasmacytoid dendritic cells in atopic dermatitis patients

摘要

Background: Dendritic cells (DCs) can act both as innate cells in host defense and as antigen-presenting cells for naive T cells in adaptive immunity. These functions, among others, are determined by the level of production of particular cytokines. Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by an initial phase predominated by T_H2 cytokines that switches into a second, more chronic T_H1-dominated eczematous phase.Objective: To assess to what extent the AD phenotype is associated with an aberrant phenotype and function of DCs. Methods: Classic CD1c~+/blood DC antigen (BDCA)-1~+ myeloid (m) DCs and CD304~+/BDCA4~+ plasmacytoid (p) DCs, the natural IFN-producing cells, were isolated from peripheral blood of patients with AD and healthy controls and analyzed for their phenotype and function.Results: Purified CD1c~+/BDCA1~+ mDCs from patients with AD showed a selective and dramatic reduction of IL-12p70 and TNF-alpha release. IL-12p70 reduction was attributed to a defectiveexpression of both IL-12p35 and IL-12p40 subunits. Accordingly, mature CDlc~+/BDCAl~+ mDCs from patients with AD induced considerably less IFN-7-producing and more IL-4-producing T_H cells compared with mDCs from healthy controls. In addition, CD304~+/BDCA4~+ pDCs from patients with AD produced significantly lower levels of IFN-alpha compared with healthy controls.Conclusion: Myeloid DCs and pDCs from patients with AD show defective IL-12, TNF-alpha, and IFN-alpha production, which may contribute to increased susceptibility to infection and to the maintenance of the T_H2 cell-mediated allergic state in patients with AD