Title: Interleukin-19: a constituent of the regulome that controls antigen presenting cells in the lungs and airway responses to microbial products.
Authors: Hoffman, Carol; Park, Sung-Hyun; Daley, Eleen; Emson, Claire; Louten, Jennifer; Sisco, Maureen; de Waal Malefyt, Rene; Grunig, Gabriele
Published In PLoS One, (2011)
Abstract: Interleukin (IL)-19 has been reported to enhance chronic inflammatory diseases such as asthma but the in vivo mechanism is incompletely understood. Because IL-19 is produced by and regulates cells of the monocyte lineage, our studies focused on in vivo responses of CD11c positive (CD11c+) alveolar macrophages and lung dendritic cells.IL-19-deficient (IL-19-/-) mice were studied at baseline (naïve) and following intranasal challenge with microbial products, or recombinant cytokines. Naïve IL-19-/- mixed background mice had a decreased percentage of CD11c+ cells in the bronchoalveolar-lavage (BAL) due to the deficiency in IL-19 and a trait inherited from the 129-mouse strain. BAL CD11c+ cells from fully backcrossed IL-19-/- BALB/c or C57BL/6 mice expressed significantly less Major Histocompatibility Complex class II (MHCII) in response to intranasal administration of lipopolysaccharide, Aspergillus antigen, or IL-13, a pro-allergic cytokine. Neurogenic-locus-notch-homolog-protein-2 (Notch2) expression by lung monocytes, the precursors of BAL CD11c+ cells, was dysregulated: extracellular Notch2 was significantly decreased, transmembrane/intracellular Notch2 was significantly increased in IL-19-/- mice relative to wild type. Instillation of recombinant IL-19 increased extracellular Notch2 expression and dendritic cells cultured from bone marrow cells in the presence of IL-19 showed upregulated extracellular Notch2. The CD205 positive subset among the CD11c+ cells was 3-5-fold decreased in the airways and lungs of naïve IL-19-/- mice relative to wild type. Airway inflammation and histological changes in the lungs were ameliorated in IL-19-/- mice challenged with Aspergillus antigen that induces T lymphocyte-dependent allergic inflammation but not in IL-19-/- mice challenged with lipopolysaccharide or IL-13.Because MHCII is the molecular platform that displays peptides to T lymphocytes and Notch2 determines cell fate decisions, our studies suggest that endogenous IL-19 is a constituent of the regulome that controls both processes in vivo.
PubMed ID: 22110701
MeSH Terms: Animals; Antigen-Presenting Cells/cytology*; Antigen-Presenting Cells/immunology; Antigen-Presenting Cells/metabolism; Antigen-Presenting Cells/microbiology*; Antigens, CD/metabolism; Antigens, Fungal/immunology; Aspergillus/physiology; Bronchoalveolar Lavage Fluid/cytology; Bronchoalveolar Lavage Fluid/immunology; Bronchoalveolar Lavage Fluid/microbiology; CD11 Antigens/metabolism; Gene Expression Regulation/immunology; HLA-D Antigens/metabolism; Interleukin-10/deficiency; Interleukin-10/metabolism*; Lectins, C-Type/metabolism; Lung/cytology; Lung/immunology*; Mice; Minor Histocompatibility Antigens; Monocytes/cytology; Monocytes/immunology; Monocytes/metabolism; Monocytes/microbiology; Receptor, Notch2/metabolism; Receptors, Cell Surface/metabolism; Species Specificity; T-Lymphocytes/cytology; T-Lymphocytes/immunology; T-Lymphocytes/metabolism; T-Lymphocytes/microbiology