title: Interleukin-19: a constituent of the regulome that controls antigen presenting cells in the lungs and airway responses to microbial products.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, United States of America.
authors: Carol
authors: C
authors: Hoffman
authors: Sung-Hyun
authors: SH
authors: Park
authors: Eleen
authors: E
authors: Daley
authors: Claire
authors: C
authors: Emson
authors: Jennifer
authors: J
authors: Louten
authors: Maureen
authors: M
authors: Sisco
authors: Rene
authors: R
authors: de Waal Malefyt
authors: Gabriele
authors: G
authors: Grunig
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D015703:Antigens, CD / Q000378:metabolism; D000946:Antigens, Fungal / Q000276:immunology; D001230:Aspergillus / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D018845:CD11 Antigens / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006681:HLA-D Antigens / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency / Q000378:metabolism*; D007378:Interleukins; D037181:Lectins, C-Type / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology*; D051379:Mice; D015778:Minor Histocompatibility Antigens; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051883:Receptor, Notch2 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D015703:Antigens, CD; D000946:Antigens, Fungal; D018845:CD11 Antigens; C093569:DEC-205 receptor; D006681:HLA-D Antigens; C498891:Il19 protein, mouse; D007378:Interleukins; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D016753:Interleukin-10