TY - JOUR
T1 - Interleukin 17A and IL-17F Expression and Functional Responses in Rheumatoid Arthritis and Peripheral Spondyloarthritis
AU - Chen, Sijia
AU - Blijdorp, Iris C.
AU - van Mens, Leonieke J. J.
AU - Bowcutt, Rowann
AU - Latuhihin, Talia E.
AU - van de Sande, Marleen G. H.
AU - Shaw, Stevan
AU - Yeremenko, Nataliya G.
AU - Baeten, Dominique L. P.
N1 - Funding Information: Dr. Baeten is supported by a VICI grant from the Netherlands Organization for Scientific Research, a consolidator grant from the European Research Council, and grants from the Dutch Arthritis Foundation Reumafonds. 1S. Chen, MD, PhD, Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and Immunology Center, University of Amsterdam, Amsterdam, Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands, and Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; 2I.C. Blijdorp, BSc, T.E. Latuhihin, BSc, N.G. Yeremenko, PhD, Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and Immunology Center, University of Amsterdam, Amsterdam, and Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 3L.J. van Mens, MD, PhD, M.G. van de Sande, MD, PhD, Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and Immunology Center, University of Amsterdam, Amsterdam, the Netherlands; 4R. Bowcutt, PhD, S. Shaw, PhD, New Medicines, UCB Pharma, Slough, UK; 5D.L. Baeten, MD, PhD, Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and Immunology Center, University of Amsterdam, Amsterdam, Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands, and New Medicines, UCB Pharma, Slough, UK. S. Chen, I.C. Blijdorp, N.G. Yeremenko, and D.L. Baeten contributed equally to this report. Address correspondence to Dr. D. Baeten, Clinical Immunology and Rheumatology, F4-105, Amsterdam University Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Email: d.l.baeten@amc.uva.nl. Accepted for publication December 10, 2019. Publisher Copyright: © 2020 Journal of Rheumatology. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Objective. Targeting the interleukin 17 (IL-17) axis is efficacious in psoriasis and spondyloarthritis (SpA), but not in rheumatoid arthritis (RA). We investigated potential differences in tissue expression and function of IL-17A and IL-17F in these conditions. Methods. mRNA expression of cytokines and their receptors was assessed by quantitative PCR in psoriasis skin samples, in SpA and RA synovial tissue (ST) samples and in fibroblast-like synoviocytes (FLS). Cytokines were measured in synovial fluid (SF) and FLS supernatants by ELISA. FLS were stimulated with IL-17A or IL-17F cytokines supplemented with tumor necrosis factor (TNF), or with pooled SF from patients with SpA or RA. Results. Levels of IL-17A (P = 0.031) and IL-17F (P = 0.017) mRNA were lower in psoriatic arthritis ST compared to paired psoriasis skin samples. The level of IL-17A mRNA was 2.7-fold lower than that of IL-17F in skin (P = 0.0078), but 17.3-fold higher in ST (P < 0.0001). In SF, the level of IL-17A protein was 37.4-fold higher than that of IL-17F [median 292.4 (IQR 81.4-464.2) vs median 7.8 (IQR 7.7-8.7) pg/mL; P < 0.0001]. IL-17A and IL-17F mRNA and protein levels did not differ in SpA compared to RA synovitis samples, and neither were the IL-17 receptors IL-17RA and IL-17RC, or the TNF receptors TNFR1 and TNR2, differentially expressed between SpA and RA ST, nor between SpA and RA FLS. SpA and RA FLS produced similar amounts of IL-6 and IL-8 protein upon stimulation with IL-17A or IL-17F cytokines, supplemented with 1 ng/ml TNF. Pooled SpA or RA SF samples similarly enhanced the inflammatory response to IL-17A and IL-17F simulation in FLS. Conclusion. The IL-17A/IL-17F expression ratio is higher in SpA synovitis compared to psoriasis skin. Expression of IL-17A and IL-17F, and the functional response to these cytokines, appear to be similar in SpA and RA synovitis.
AB - Objective. Targeting the interleukin 17 (IL-17) axis is efficacious in psoriasis and spondyloarthritis (SpA), but not in rheumatoid arthritis (RA). We investigated potential differences in tissue expression and function of IL-17A and IL-17F in these conditions. Methods. mRNA expression of cytokines and their receptors was assessed by quantitative PCR in psoriasis skin samples, in SpA and RA synovial tissue (ST) samples and in fibroblast-like synoviocytes (FLS). Cytokines were measured in synovial fluid (SF) and FLS supernatants by ELISA. FLS were stimulated with IL-17A or IL-17F cytokines supplemented with tumor necrosis factor (TNF), or with pooled SF from patients with SpA or RA. Results. Levels of IL-17A (P = 0.031) and IL-17F (P = 0.017) mRNA were lower in psoriatic arthritis ST compared to paired psoriasis skin samples. The level of IL-17A mRNA was 2.7-fold lower than that of IL-17F in skin (P = 0.0078), but 17.3-fold higher in ST (P < 0.0001). In SF, the level of IL-17A protein was 37.4-fold higher than that of IL-17F [median 292.4 (IQR 81.4-464.2) vs median 7.8 (IQR 7.7-8.7) pg/mL; P < 0.0001]. IL-17A and IL-17F mRNA and protein levels did not differ in SpA compared to RA synovitis samples, and neither were the IL-17 receptors IL-17RA and IL-17RC, or the TNF receptors TNFR1 and TNR2, differentially expressed between SpA and RA ST, nor between SpA and RA FLS. SpA and RA FLS produced similar amounts of IL-6 and IL-8 protein upon stimulation with IL-17A or IL-17F cytokines, supplemented with 1 ng/ml TNF. Pooled SpA or RA SF samples similarly enhanced the inflammatory response to IL-17A and IL-17F simulation in FLS. Conclusion. The IL-17A/IL-17F expression ratio is higher in SpA synovitis compared to psoriasis skin. Expression of IL-17A and IL-17F, and the functional response to these cytokines, appear to be similar in SpA and RA synovitis.
KW - Interleukin 17A
KW - Interleukin 17F
KW - Rheumatoid arthritis
KW - Spondyloarthritis
KW - Synovial fibroblasts
KW - Therapeutic targeting
UR - http://www.scopus.com/inward/record.url?scp=85095460967&partnerID=8YFLogxK
U2 - https://doi.org/10.3899/jrheum.190571
DO - https://doi.org/10.3899/jrheum.190571
M3 - Article
C2 - 31941804
SN - 0315-162X
VL - 47
SP - 1606
EP - 1613
JO - Journal of rheumatology
JF - Journal of rheumatology
IS - 11
ER -