title: A thymic stromal lymphopoietin-responsive dendritic cell subset mediates allergic responses in the upper airway mucosa.
abstract: BACKGROUND
  Thymic stromal lymphopoietin (TSLP) controls allergic TH2 inflammatory responses through induction of distinct activation programs in dendritic cells (DCs). However, knowledge about TSLP receptor expression and functional consequences of receptor activation by DCs residing in the human respiratory tract is limited.
  
  
  OBJECTIVE
  We wanted to identify TSLP-responding DC populations in the human upper airway mucosa and assess the TSLP-mediated effects on such DCs in allergic airway responses.
  
  
  RESULTS
  We found that the TSLP receptor was constitutively and preferentially expressed by myeloid CD1c(+) DCs in the human airway mucosa and that the density of this DC subset in nasal mucosa increased significantly after in vivo allergen challenge of patients with allergic rhinitis. In vitro, TSLP strongly enhanced the capacity of CD1c(+) DCs to activate allergen-specific memory CD4(+) T cells. Moreover, TSLP rapidly induced CCR7 expression on CD1c(+) DCs. However, TH2 cytokines attenuated TSLP-mediated CCR7 induction, thus inhibiting the TSLP-induced DC migration potential to the draining lymph nodes.
  
  
  CONCLUSIONS
  Our results suggest that TSLP-mediated activation of human nasal mucosal CD1c(+) DCs triggers CCR7-dependent migration to the draining lymph nodes and enhances their capacity to initiate TH2 responses. However, the observation that TH2 cytokines abrogate the induction of CCR7 implies that during a TH2-mediated inflammatory reaction, TLSP-activated CD1c(+) DCs are retained in the inflamed tissue to further exacerbate local inflammation by activating local antigen-specific memory TH2 cells.
authors: Department of Pathology, Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway; Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway. Electronic address: guro.reinholt.melum@rr-research.no.
authors: Guro R
authors: GR
authors: Melum
authors: Department of Pathology, Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors: Lorant
authors: L
authors: Farkas
authors: Department of Pathology, Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors: Cecilie
authors: C
authors: Scheel
authors: Department of Pathology, Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway; Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors: Brenda
authors: B
authors: Van Dieren
authors: Department of Otolaryngology, Lovisenberg Diakonale Hospital, Oslo, Norway.
authors: Einar
authors: E
authors: Gran
authors: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Tex.
authors: Yong-Jun
authors: YJ
authors: Liu
authors: Department of Pathology, Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway; Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors: Finn-Eirik
authors: FE
authors: Johansen
authors: Department of Pathology, Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway; Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors: Frode L
authors: FL
authors: Jahnsen
authors: Department of Pathology, Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway; Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors: Espen S
authors: ES
authors: Baekkevold
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology; D018949:Antigens, CD1 / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology*; D065631:Rhinitis, Allergic / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000485:Allergens; D018949:Antigens, CD1; C515370:CCR7 protein, human; C437944:CD1C protein, human; C498762:CRLF2 protein, human; D016207:Cytokines; D006023:Glycoproteins; D054400:Receptors, CCR7; D018121:Receptors, Cytokine; D000094632:Thymic Stromal Lymphopoietin
keywords: CCR7; Thymic stromal lymphopoietin; airway allergy; dendritic cells; human airway mucosa