Development of proteoglycan-induced arthritis is independent of IL-17.
IL-17 is the hallmark cytokine for the newly identified subset of Th cells, Th17. Th17 cells are important instigators of inflammation in several models of autoimmune disease; in particular, collagen induced arthritis (CIA) and experimental autoimmune encephalomyelitis (EAE), which were previously characterized as Th1-mediated diseases. Although high levels of IFN-gamma are secreted in CIA and EAE, disease is exacerbated in IFN-gamma- or IFN-gamma receptor-deficient mice due to the ability of IFN-gamma to suppress IL-17 secretion. However, in proteoglycan-induced arthritis (PGIA), severe arthritis is dependent on the production of IFN-gamma. We were therefore interested in determining the role of IL-17 in PGIA. We assessed the progression of arthritis in IL-17-deficient (IL-17-/-) mice and found the onset and severity of arthritis were equivalent in wild-type (WT) and IL-17-/- mice. Despite evidence that IL-17 is involved in neutrophil recruitment, synovial fluid from arthritic joints showed a comparable proportion of Gr1+ neutrophils in WT and IL-17-/- mice. IL-17 is also implicated in bone destruction in autoimmune arthritis, however, histological analysis of the arthritic joints from WT and IL-17-/- mice revealed a similar extent of joint cellularity, cartilage destruction, and bone erosion despite significantly reduced RANKL (receptor activator of NK-kappaB ligand) expression. There were only subtle differences between WT and IL-17-/- mice in proinflammatory cytokine expression, T cell proliferation, and autoantibody production. These data demonstrate that IL-17 is not absolutely required for autoimmune arthritis and that the production of other proinflammatory mediators is sufficient to compensate for the loss of IL-17 in PGIA.
Doodes
Paul D
PD
Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
Cao
Yanxia
Y
Hamel
Keith M
KM
Wang
Yumei
Y
Farkas
Balint
B
Iwakura
Yoichiro
Y
Finnegan
Alison
A
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001847:Bone Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011509:Proteoglycans / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
D020381:Interleukin-17; D011509:Proteoglycans; D053245:RANK Ligand; D018664:Interleukin-12; D007371:Interferon-gamma