title: TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosis.
abstract: BACKGROUND
  TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place.
  
  
  METHODS
  In this study, by flow cytometry, real-time PCR, confocal microscopy and immunohistochemistry analyses, TL1A and DR3 were investigated in the pulmonary cells and the peripheral blood of 43 patients affected by sarcoidosis in different phases of the disease (29 patients with active sarcoidosis, 14 with the inactive form) and in 8 control subjects.
  
  
  RESULTS
  Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls. In patients with sarcoidosis TL1A was strongly more expressed in the lung than the blood, i.e., at the site of the involved organ. Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1.
  
  
  CONCLUSIONS
  These data suggest that TL1A/DR3 interactions are part of the extended and complex immune-inflammatory network that characterizes sarcoidosis during its active phase and may contribute to the pathogenesis and to the progression of the disease.
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy ; Venetian Institute of Molecular Medicine, Padua, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Facco
authors.affiliation: Venetian Institute of Molecular Medicine, Padua, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cabrelle
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, Padua University School of Medicine, Padua, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Calabrese
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy ; Venetian Institute of Molecular Medicine, Padua, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Teramo
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cinetto
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Carraro
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy ; Venetian Institute of Molecular Medicine, Padua, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Martini
authors.affiliation: Department of Pathology and Diagnostics, Section of General Pathology, School of Medicine, University of Verona, Verona, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Calzetti
authors.affiliation: Department of Pathology and Diagnostics, Section of General Pathology, School of Medicine, University of Verona, Verona, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Tamassia
authors.affiliation: Department of Pathology and Diagnostics, Section of General Pathology, School of Medicine, University of Verona, Verona, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Cassatella
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy ; Venetian Institute of Molecular Medicine, Padua, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Semenzato
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy ; Venetian Institute of Molecular Medicine, Padua, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Agostini
keywords: Lung; MMP-9; Sarcoidosis; TIMP-1; TL1A/DR3; TNF family members