Soluble TNF-like cytokine (TL1A) production by immune complexes stimulated monocytes in rheumatoid arthritis.
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.
Cassatella
Marco A
MA
Department of Pathology, Division of General Pathology, University of Verona, Verona, Italy. marco.cassatella@univr.it
Pereira-da-Silva
Gabriela
G
da Silva
Gabriela Pereira
GP
Tinazzi
Ilaria
I
Facchetti
Fabio
F
Scapini
Patrizia
P
Calzetti
Federica
F
Tamassia
Nicola
N
Wei
Ping
P
Nardelli
Bernardetta
B
Roschke
Viktor
V
Vecchi
Annunciata
A
Mantovani
Alberto
A
Bambara
Lisa M
LM
Edwards
Steven W
SW
Carletto
Antonio
A
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
D000936:Antigen-Antibody Complex; D016207:Cytokines; D017452:Receptors, IgG; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D011092:Polyethylene Glycols