IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis.
The origin and role of IL-17, a T-cell derived cytokine, in cartilage and bone destruction during rheumatoid arthritis (RA) remain to be clarified. In human ex vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction, and inhibited collagen synthesis by RA synovium explants. On mouse cartilage, IL-17 enhanced cartilage proteoglycan loss and inhibited its synthesis. On human RA bone explants, IL-17 also increased bone resorption and decreased formation. Addition of IL-1 in these conditions increased the effect of IL-17. Blocking of bone-derived endogenous IL-17 with specific inhibitors resulted in a protective inhibition of bone destruction. Conversely, intra-articular administration of IL-17 into a normal mouse joint induced cartilage degradation. In conclusion, the contribution of IL-17 derived from synovium and bone marrow T cells to joint destruction suggests the control of IL-17 for the treatment of RA.
Chabaud
M
M
INSERM U403, Faculté de Médecine Laennec, and Departments of Immunology and Rheumatology, Hôpital Edouard Herriot, Lyon, France.
Lubberts
E
E
Joosten
L
L
van Den Berg
W
W
Miossec
P
P
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D007270:Injections, Intra-Articular; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D020381:Interleukin-17 / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000096:biosynthesis; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D007375:Interleukin-1; D020381:Interleukin-17; D015850:Interleukin-6; D011509:Proteoglycans; D007334:Insulin-Like Growth Factor I; D003094:Collagen