title: Evidence for local dendritic cell activation in pulmonary sarcoidosis.
abstract: BACKGROUND
  Sarcoidosis is a granulomatous disease characterized by a seemingly exaggerated immune response against a difficult to discern antigen. Dendritic cells (DCs) are pivotal antigen presenting cells thought to play an important role in the pathogenesis. Paradoxically, decreased DC immune reactivity was reported in blood samples from pulmonary sarcoidosis patients. However, functional data on lung DCs in sarcoidosis are lacking. We hypothesized that at the site of disease DCs are mature, immunocompetent and involved in granuloma formation.
  
  
  METHODS
  We analyzed myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in broncho-alveolar lavage (BAL) and blood from newly diagnosed, untreated pulmonary sarcoidosis patients and healthy controls using 9-color flowcytometry. DCs, isolated from BAL using flowcytometric sorting (mDCs) or cultured from monocytes (mo-DCs), were functionally assessed in a mixed leukocyte reaction with naïve allogeneic CD4+ T cells. Using Immunohistochemistry, location and activation status of CD11c+DCs was assessed in mucosal airway biopsies.
  
  
  RESULTS
  mDCs in BAL, but not in blood, from sarcoidosis patients were increased in number when compared with mDCs from healthy controls. mDCs purified from BAL of sarcoidosis patients induced T cell proliferation and differentiation and did not show diminished immune reactivity. Mo-DCs from patients induced increased TNFα release in co-cultures with naïve allogeneic CD4+ T cells. Finally, immunohistochemical analyses revealed increased numbers of mature CD86+ DCs in granuloma-containing airway mucosal biopsies from sarcoidosis patients.
  
  
  CONCLUSIONS
  Taken together, these finding implicate increased local DC activation in granuloma formation or maintenance in pulmonary sarcoidosis.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Bregje
authors.initials: B
authors.lastname: Ten Berge
authors.forename: Alex
authors.initials: A
authors.lastname: Kleinjan
authors.forename: Femke
authors.initials: F
authors.lastname: Muskens
authors.forename: Hamida
authors.initials: H
authors.lastname: Hammad
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: Bernt
authors.initials: B
authors.lastname: Van den Blink
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D002452:Cell Count; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D005260:Female; D006099:Granuloma / Q000473:pathology*; D006801:Humans; D008168:Lung / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000473:pathology; D017565:Sarcoidosis, Pulmonary / Q000097:blood / Q000473:pathology*; D055815:Young Adult