title: Rapid recruitment of CD14(+) monocytes in experimentally induced allergic rhinitis in human subjects.
abstract: Activated TH2 cells and eosinophils are hallmarks of the allergic inflammation seen in patients with allergic rhinitis (AR). However, which cells activate and attract T cells and eosinophils to the inflammatory lesion has not been determined.
  
  
  
  We wanted to assess the role of mucosal mononuclear phagocytes, consisting of monocytes, macrophages, and dendritic cells, in the local allergic inflammatory reaction.
  
  
  
  Patients with AR and nonatopic control subjects were challenged with pollen extract, and nasal symptoms were recorded. Mucosal biopsy specimens obtained at different time points before and after challenge were used for immunostaining in situ and flow cytometric cell sorting. Sorted mononuclear phagocytes were subjected to RNA extraction and gene expression profiling.
  
  
  
  In an in vivo model of AR, we found that CD14(+) monocytes were recruited to the nasal mucosa within hours after local allergen challenge, whereas conventional dendritic cells accumulated after several days of continued provocation. Transcriptomic profiling of mucosal mononuclear phagocytes sorted after 1 week of continued allergen challenge showed an activated phenotype at least partially driven by IL-4 signaling, IL-13 signaling, or both. Importantly, gene expression of several TH2-related chemokines was significantly upregulated by the mononuclear phagocyte population concomitant with an increased recruitment of CD4(+) T cells and eosinophils.
  
  
  
  Our findings suggest that the mononuclear phagocyte population is directly involved in the production of proinflammatory chemokines that attract other immune cells. Rapid recruitment of CD14(+) monocytes to the challenged site indicates that these proinflammatory mononuclear phagocytes have a central role in orchestrating local allergic inflammation.
authors: Department of Pathology and Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors: Ibon
authors: I
authors: Eguíluz-Gracia
authors: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors: Anthony
authors: A
authors: Bosco
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway; Department of Otorhinolaryngology, Head and Neck Surgery, Universitätsmedizin Mannheim-Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Ralph
authors: R
authors: Dollner
authors: Department of Pathology and Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors: Guro Reinholt
authors: GR
authors: Melum
authors: Department of Pathology and Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors: Maria H
authors: MH
authors: Lexberg
authors: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors: Anya C
authors: AC
authors: Jones
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors: Sinan Ahmed
authors: SA
authors: Dheyauldeen
authors: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors: Patrick G
authors: PG
authors: Holt
authors: Department of Pathology and Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors: Espen S
authors: ES
authors: Bækkevold
authors: Department of Pathology and Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway. Electronic address: frode.lars.jahnsen@rr-research.no.
authors: Frode Lars
authors: FL
authors: Jahnsen
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D001706:Biopsy; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D065631:Rhinitis, Allergic / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors
keywords: CD14(+) monocytes; T(H)2-associated chemokines; dendritic cells; human airway allergy; nasal mucosa; resident macrophages