title: Soluble TNF-like cytokine (TL1A) production by immune complexes stimulated monocytes in rheumatoid arthritis.
abstract: TNF-like cytokine (TL1A) is a newly identified member of the TNF superfamily of ligands that is important for T cell costimulation and Th1 polarization. However, despite increasing information about its functions, very little is known about expression of TL1A in normal or pathological states. In this study, we report that mononuclear phagocytes appear to be a major source of TL1A in rheumatoid arthritis (RA), as revealed by their strong TL1A expression in either synovial fluids or synovial tissue of rheumatoid factor (RF)-seropositive RA patients, but not RF-/RA patients. Accordingly, in vitro experiments revealed that human monocytes express and release significant amounts of soluble TL1A when stimulated with insoluble immune complexes (IC), polyethylene glycol precipitates from the serum of RF+/RA patients, or with insoluble ICs purified from RA synovial fluids. Monocyte-derived soluble TL1A was biologically active as determined by its capacity to induce apoptosis of the human erythroleukemic cell line TF-1, as well as to cooperate with IL-12 and IL-18 in inducing the production of IFN-gamma by CD4(+) T cells. Because RA is a chronic inflammatory disease with autoimmune etiology, in which ICs, autoantibodies (including RF), and various cytokines contribute to its pathology, our data suggest that TL1A could be involved in its pathogenesis and contribute to the severity of RA disease that is typical of RF+/RA patients.
authors.affiliation: Department of Pathology, Division of General Pathology, University of Verona, Verona, Italy. marco.cassatella@univr.it
authors.forename: Marco A
authors.initials: MA
authors.lastname: Cassatella
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pereira-da-Silva
authors.forename: Gabriela Pereira
authors.initials: GP
authors.lastname: da Silva
authors.forename: Ilaria
authors.initials: I
authors.lastname: Tinazzi
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Scapini
authors.forename: Federica
authors.initials: F
authors.lastname: Calzetti
authors.forename: Nicola
authors.initials: N
authors.lastname: Tamassia
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Bernardetta
authors.initials: B
authors.lastname: Nardelli
authors.forename: Viktor
authors.initials: V
authors.lastname: Roschke
authors.forename: Annunciata
authors.initials: A
authors.lastname: Vecchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Bambara
authors.forename: Steven W
authors.initials: SW
authors.lastname: Edwards
authors.forename: Antonio
authors.initials: A
authors.lastname: Carletto
mesh_terms: D000936:Antigen-Antibody Complex / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation; D009000:Monocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D011092:Polyethylene Glycols / Q000378:metabolism; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000502:physiology; D012995:Solubility; D013582:Synovial Fluid / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D013583:Synovial Membrane / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism / Q000502:physiology
chemical_list: D000936:Antigen-Antibody Complex; D016207:Cytokines; D017452:Receptors, IgG; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D011092:Polyethylene Glycols