ABSTRACT
Dendritic cells (DCs) are specific antigen-presenting cells that play critical roles in the initiation and polarization of immune responses. DCs residing in the lungs might be detected in the bronchoalveolar lavage fluid (BALF). We analysed DC compartment in the peripheral blood and BALF of patients with allergy and in controls. Plasmacytoid and four distinct subsets of myeloid DCs [characterized by the expression of blood dendritic cell antigen (BDCA)-1+ and -3+ and CD16 positivity or negativity] were detected in both tested compartments. We further evaluated the expression of C-type lectins [mannose receptor (MR), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and dendritic and epithelial cells (DEC)-205] relevant to the pathogenesis of asthma. Interestingly, we found a selective increase in the frequency of myeloid DC-expressing BDCA-3 and MR particularly in BALF from allergic patients. Specific and highly statistically significant increase in BDCA-3+ and/or MR+ DCs brings a novel characteristic to BAL analysis in allergic patients.
Subject(s)
Asthma/immunology , Bronchoalveolar Lavage Fluid/immunology , Cell Adhesion Molecules/immunology , Dendritic Cells/immunology , Lectins, C-Type/immunology , Receptors, Cell Surface/immunology , Adult , Asthma/blood , Bronchoalveolar Lavage Fluid/cytology , Cell Adhesion Molecules/blood , Child , Dendritic Cells/cytology , Female , Flow Cytometry , GPI-Linked Proteins/blood , GPI-Linked Proteins/immunology , Humans , Immunophenotyping/methods , Lectins, C-Type/blood , Lung/cytology , Lung/immunology , Male , Receptors, Cell Surface/blood , Receptors, IgG/blood , Receptors, IgG/immunology , Statistics, NonparametricABSTRACT
Hyper-immunoglobulin (Ig)E syndrome (HIES) is a primary immunodeficiency associated with mutations in STAT3 resulting in impaired development of T helper type 17 (Th17) lymphocytes. HIES patients with a reduced frequency of Th17 cells present with infections caused by Staphylococcus aureus and/or Candida strains. The same spectrum of pathogens is present in patients with chronic granulomatous disease (CGD).We analysed the characteristics of the Th17 compartment in HIES and CGD. HIES patients showed very low numbers of Th17 cells. By contrast, the frequency of Th17 cells and production of Th17-derived cytokines was significantly higher among CGD patients when compared to both control samples and HIES. Naive CD4(+) cells in CGD patients had a normal capacity to differentiate into IL-17-producing cells and the numbers of Th17 cells in the CGD patients normalized following successful bone marrow transplantation. Our findings complement recent data on the importance of Th17 cells for elimination of infections with C. albicans and S. aureus.
Subject(s)
Granulomatous Disease, Chronic/immunology , Interferon-gamma/immunology , Interleukin-17/immunology , Job Syndrome/immunology , Membrane Glycoproteins/immunology , NADPH Oxidases/immunology , STAT3 Transcription Factor/immunology , Th17 Cells/immunology , Adult , Candida albicans/growth & development , Candidiasis/immunology , Candidiasis/microbiology , Case-Control Studies , Cell Differentiation/immunology , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Granulomatous Disease, Chronic/genetics , Granulomatous Disease, Chronic/metabolism , Granulomatous Disease, Chronic/pathology , Granulomatous Disease, Chronic/therapy , Hematopoietic Stem Cell Transplantation , Humans , Interferon-gamma/metabolism , Interleukin-17/metabolism , Job Syndrome/genetics , Job Syndrome/metabolism , Job Syndrome/pathology , Lymphocyte Count , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Mutation , NADPH Oxidase 2 , NADPH Oxidases/genetics , NADPH Oxidases/metabolism , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Staphylococcal Infections/immunology , Staphylococcal Infections/microbiology , Staphylococcus aureus/growth & development , Th17 Cells/metabolism , Th17 Cells/pathology , Transplantation, HomologousABSTRACT
BACKGROUND: Dendritic cells represent the most effective antigen presenting cells and they are the only cell type capable of initiating the primary immune response. They use several sets of germ-line encoded receptors to differentiate between self and non-self and to detect the presence of danger signals. Danger signals are mainly represented by microbial pathogens but it can be also a necrotic or malignant cell. At various stages of their lifecycle dendritic cells play a key role in maintaining the peripheral tolerance towards self-antigens and in the initiation of an effective immune response. Glucocorticoids have been widely used in the treatment of autoimmune or inflammatory disorders and their immunosuppressive effect has been mainly attributed to the inhibition of lymphocytes functions. METHODS AND RESULTS: In this study, we discuss the effects of glucocorticoids on in vitro generated myeloid dendritic cells and on peripheral blood myeloid and plasmacytoid dendritic cells subsets. CONCLUSIONS: Experimental results point to the profound suppressive effect of glucocorticoids on the antigen presenting functions of dendritic cells and to contribute to better understanding of glucocorticoids-mediated immunosuppressive effect.
