Impaired IL-10-dependent Induction of Tolerogenic Dendritic Cells by CD4~+ CD25~(hi)CD127~(lo/-) Natural Regulatory T Cells in Human Allergic Asthma

摘要

Rationale: Tolerogenic dendritic cells and natural regulatory T cells have been implicated in the process of infectious tolerance in human allergic asthma. However, the significance of the influence of natural regulatory T cells on tolerogenic dendritic cells in the disease has not been investigated.rnObjectives: We aimed to characterize the mechanism of induction of the tolerogenic phenotype in circulating blood dendritic cells by allergic asthmatic natural regulatory T cells.rnMethods: The study was performed in a cohort of 21 subjects with allergic asthma, 21 healthy control subjects, and 21 subjects with nonallergic asthma. We cultured blood dendritic cells with natural regulatory T cells to study the induction of tolerogenic dendritic cells. Flow cytometry and proliferation assays were employed to analyze phenotype and function of dendritic cells as well as IL-10 production from natural regulatory T cells.rnMeasurements and Main Results: Dendritic cells cultured with natural regulatory T cells up-regulated IL-10, down-regulated costimulatory molecules, and stimulated the proliferation of CD4~+CD25~- effector T cells less potently. Allergic asthmatic natural regulatory T cells were significantly less efficient in inducing this tolerogenic phenotype of dendritic cells compared with healthy control and nonallergic asthmatic counterparts. Furthermore, this defective function of natural regulatory T cells was associated with their decreased IL-10 expression, disease severity, and could be reversed by oral cortico-steroid therapy.rnConclusions: These results provided the first evidences of impaired induction of tolerogenic dendritic cells mediated by natural regulatory T cells in human allergic asthma.