title: Polymeric immunoglobulin receptor down-regulation in chronic obstructive pulmonary disease. Persistence in the cultured epithelium and role of transforming growth factor-β.
abstract: BACKGROUND
  The generation of protective secretory IgA relies on the epithelial polymeric immunoglobulin receptor (pIgR). pIgR expression is reduced in chronic obstructive pulmonary disease (COPD), but correlation to disease severity and underlying mechanisms remains unknown.
  
  
  OBJECTIVE
  To address the hypothesis that pIgR down-regulation in COPD concerns severe disease in relation to aberrant programming of the bronchial epithelium.
  
  
  METHODS
  Surgical lung tissue and primary bronchial epithelium (cultured in air-liquid interface, ALI) obtained from a large series of patients (n = 116) were studied for pIgR expression and regulation.
  
  
  RESULTS
  pIgR immunostaining in the bronchial epithelium is decreased in severe COPD. In contrast, pIgR transcription was up-regulated in smokers with or without COPD. In ALI (vs. submerged) cultures, pIgR expression was strongly induced, whereas pIgR expression and IgA-transcytosis capacity were decreased in cultures from subjects with severe COPD as compared with control subjects. In addition, COPD cultures released more transforming growth factor-β1 (TGF-β1), reflecting increased epithelial TGF-β1 immunostaining in COPD lung tissue. Finally, besides inducing epithelial dedifferentiation, exogenous TGF-β1 dose-dependently inhibited pIgR production, whereas pIgR increased on blockade of TGF-β1 activity during ALI differentiation.
  
  
  CONCLUSIONS
  pIgR down-regulation in COPD correlates with disease severity, and the bronchial epithelium reconstituted in vitro from these patients retains its aberrant imprinting for pIgR expression. This study also links pIgR down-regulation to TGF-β-driven reprogramming of the bronchial epithelium, which results in impaired lung IgA immunity in patients with COPD.
authors: 1 Pole of Pneumology, ENT, and Dermatology, and.
authors: Sophie T
authors: ST
authors: Gohy
authors: Bruno R
authors: BR
authors: Detry
authors: Marylène
authors: M
authors: Lecocq
authors: Caroline
authors: C
authors: Bouzin
authors: Birgit A
authors: BA
authors: Weynand
authors: Gimano D
authors: GD
authors: Amatngalim
authors: Yves M
authors: YM
authors: Sibille
authors: Charles
authors: C
authors: Pilette
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism*; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D019056:Receptors, Polymeric Immunoglobulin / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*; D012720:Severity of Illness Index; D012907:Smoking / Q000378:metabolism; D046509:Tissue Culture Techniques; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D019056:Receptors, Polymeric Immunoglobulin; D053773:Transforming Growth Factor beta1
keywords: IgA; chronic obstructive pulmonary disease; immunology