ABSTRACT
BACKGROUND: Dendritic cells (DCs) are crucial for the induction of immunity and tolerance. Despite an improved understanding of the DC-mediated control of T(H)1-biased immunity, little is known about how DCs regulate T(H)2-mediated immunity. OBJECTIVE: The effects of immunostimulatory mature DCs (maDCs) and regulatory DCs (DCregs) on T(H)2-driven allergic immunity involving IgE production were examined. METHODS: A murine model of airway hyperresponsiveness; the adoptive transfer of maDCs, DCregs, and T cells; and T-cell function were studied. RESULTS: Antigen-pulsed maDCs inhibited antigen-specific IgE production but enhanced the production of antigen-specific IgG1 and IgG2a. Analysis of Ifng-/- mice and Il21r-/- mice revealed that the inhibitory effect of antigen-pulsed maDCs on antigen-specific IgE production involved IL-21-producing T follicular helper cells but not IFN-gamma-producing T(H)1 cells. In contrast, antigen-pulsed DCregs impaired the production of antigen-specific IgE, IgG1, and IgG2a. In vivo blockade experiments showed that antigen-specific CD4+CD25+Foxp3+ regulatory T cells mainly mediated the suppressive effect of antigen-pulsed DCregs on the production of antigen-specific IgE. Antigen-pulsed maDCs promoted airway inflammation, whereas antigen-pulsed DCregs markedly suppressed the pathogenesis. CONCLUSION: DCregs abolish T(H)2-mediated IgE production and allergic inflammation based on antigen-specific dominant tolerance, whereas maDCs exacerbate the pathogenesis despite inhibiting the IgE response through the activation of diverse types of T(H) cell responses.
Subject(s)
Asthma/immunology , Bronchial Hyperreactivity/immunology , Dendritic Cells/immunology , Dendritic Cells/transplantation , Disease Models, Animal , Hypersensitivity/immunology , Inflammation/immunology , Adoptive Transfer , Animals , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , T-Lymphocytes, RegulatoryABSTRACT
Annexins are a family of proteins that bind to phospholipids and carbohydrates in a calcium-dependent manner. They are present in a variety of body fluids. Previous studies have shown that annexins have anti-inflammatory activities for lipid A of Gram-negative bacteria. The present study investigated the effect of annexins on interaction between Gram-positive bacteria and immune cells such as macrophages. Annexins I and IV bound to lipoteichoic acids which are surface molecules on Gram-positive bacteria. Binding of annexins I and IV to whole Staphylococcus aureus (S. aureus) were observed and these bindings were inhibited by lipoteichoic acid from S. aureus. Moreover, annexins I and IV suppressed the attachment of S. aureus to phorbol 12-myristate 13-acetate-treated THP-1 cells (human macrophages). These results suggest that annexins I and IV have ligand specificities toward foreign substances, and that the annexins might have some anti-inflammatory property for Gram-positive bacteria.
