title: Role of the chemokine receptors CXCR3 and CCR4 in human pulmonary fibrosis.
abstract: BACKGROUND
  The chemokine receptors CXCR3 and CCR4 have recently been described as playing a pivotal role in the mouse model of bleomycin-induced fibrosis.
  
  
  OBJECTIVE
  To evaluate the role of these receptors in human idiopathic pulmonary fibrosis (IPF).
  
  
  METHODS
  We studied 57 patients: 18 with IPF, 17 with non-IPF (nIPF), 12 with sarcoidosis, and 10 healthy control subjects.
  
  
  METHODS
  We evaluated the expression of CXCR3 and CCR4 in blood and bronchoalveolar lavage (BAL) T lymphocytes by flow cytometry and the chemokine CXCL10, CXCL11 and CCL17 BAL concentration by singular immunoassay.
  
  
  RESULTS
  Patients with IPF had a significantly lower CXCR3 and a higher CCR4 expression on BAL CD4 T cells compared with the other groups. Among patients with IPF, those treated with corticosteroids exhibited higher CXCR3 and lower CCR4 expression compared with untreated patients. CXCR3 expression correlated with BAL lymphocytes and CCR4 with BAL neutrophils and eosinophils. CXCL10 levels correlated with the expression of CXCR3 on BAL CD4 cells. CXCL11 was undetectable in almost all patients, whereas CCL17 was primarily detectable in patients with IPF. The percentage of BAL CCR4CD4 cells negatively correlated with DL(CO). The changes in the total lung capacity, VC, and of the alveolar-arterial PO2 gradient in patients with IPF and those with nIPF 6 to 12 mo after the first evaluation were associated with CD4CXCR3 percentage on BAL cells.
  
  
  CONCLUSIONS
  We found an imbalance in CXCR3/CCR4 expression on BAL CD4 lymphocytes and reduced CXCL10 BAL levels in patients with IPF, suggesting a pivotal role of these molecules in IPF.
authors.affiliation: Allergy and Immunology Unit, Rehabilitative Pneumology Department, Pavia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pignatti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Brunetti
authors.forename: Dania
authors.initials: D
authors.lastname: Moretto
authors.forename: Mona-Rita
authors.initials: MR
authors.lastname: Yacoub
authors.forename: Marco
authors.initials: M
authors.lastname: Fiori
authors.forename: Bruno
authors.initials: B
authors.lastname: Balbi
authors.forename: Antonella
authors.initials: A
authors.lastname: Balestrino
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cervio
authors.forename: Stefano
authors.initials: S
authors.lastname: Nava
authors.forename: Gianna
authors.initials: G
authors.lastname: Moscato
mesh_terms: D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D054414:Chemokine CCL17; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: C106230:CCL17 protein, human; C515354:CCR4 protein, human; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C515187:CXCR3 protein, human; C515355:Ccr4 protein, mouse; D054414:Chemokine CCL17; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515203:Cxcl11 protein, mouse; C515188:Cxcr3 protein, mouse; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine