Τίτλος:
Transmembrane TNF drives osteoproliferative joint inflammation reminiscent of human spondyloarthritis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
TNF plays a key role in immune-mediated inflammatory diseases including rheumatoid arthritis (RA) and spondyloarthritis (SpA). It remains incompletely understood how TNF can lead to different disease phenotypes such as destructive peripheral polysynovitis in RA versus axial and peripheral osteoproliferative inflammation in SpA. We observed a marked increase of transmembrane (tm) versus soluble (s) TNF in SpA versus RA together with a decrease in the enzymatic activity of ADAM17. In contrast with the destructive polysynovitis observed in classical TNF overexpression models, mice overexpressing tmTNF developed axial and peripheral joint disease with synovitis, enthesitis, and osteitis. Histological and radiological assessment evidenced marked endochondral new bone formation leading to joint ankylosis over time. SpA-like inflammation, but not osteoproliferation, was dependent on TNF-receptor I and mediated by stromal tmTNF overexpression. Collectively, these data indicate that TNF can drive distinct inflammatory pathologies.We propose that tmTNF is responsible for the key pathological features of SpA. © 2020 Rockefeller University Press. All rights reserved.
Συγγραφείς:
Kaaij, M.H.
Tok, M.N.V.
Blijdorp, I.C.
Ambarus, C.A.
Stock, M.
Pots, D.
Knaup, V.L.
Armaka, M.
Christodoulou-Vafeiadou, E.
Melsen, T.K.V.
Masdar, H.
Eskes, H.J.P.P.
Yeremenko, N.G.
Kollias, G.
Schett, G.
Tas, S.W.
Duivenvoorde, L.M.V.
Baeten, D.L.P.
Περιοδικό:
JOURNAL OF EXPERIMENTAL MEDICINE
Εκδότης:
Rockefeller University Press
Λέξεις-κλειδιά:
biological marker; cytokine; membrane protein; messenger RNA; soluble tumor necrosis factor; transmembrane tumor necrosis factor; tumor necrosis factor; tumor necrosis factor alpha converting enzyme; tumor necrosis factor receptor 1; unclassified drug; Adam17 protein, mouse; Tnf protein, mouse; tumor necrosis factor; tumor necrosis factor alpha converting enzyme; tumor necrosis factor receptor, adult; animal cell; animal experiment; animal model; animal tissue; arthritis; Article; bone disease; bone erosion; cartilage degeneration; comparative study; controlled study; enchondral ossification; enthesitis; enzyme activity; female; gene overexpression; histopathology; human; human cell; human tissue; major clinical study; male; middle aged; mouse; mRNA expression level; nonhuman; osteitis; osteoproliferation; priority journal; rheumatoid arthritis; sacroiliitis; signal transduction; spine radiography; spondylarthritis; spondylitis; stroma cell; synovitis; animal; arthritis; bone development; disease model; fluorescent antibody technique; joint; metabolism; physiology; spondylarthritis; synovitis, ADAM17 Protein; Adult; Animals; Arthritis; Disease Models, Animal; Female; Fluorescent Antibody Technique; Humans; Joints; Male; Mice; Osteogenesis; Receptors, Tumor Necrosis Factor; Spondylarthritis; Synovitis; Tumor Necrosis Factor-alpha
DOI:
10.1084/JEM.20200288
