Polymerized-type I collagen induces upregulation of Foxp3-expressing CD4 regulatory T cells and downregulation of IL-17-producing CD4⁺ T cells (Th17) cells in collagen-induced arthritis
Janette Furuzawa-Carballeda, Perla Macip-Rodríguez, Angeles S Galindo-Feria, David Cruz-Robles, Virgina Soto-Abraham, Sergio Escobar-Hernández, Diana Aguilar, Deshiré Alpizar-Rodríguez, Karen Férez-Blando, Luis Llorente, Janette Furuzawa-Carballeda, Perla Macip-Rodríguez, Angeles S Galindo-Feria, David Cruz-Robles, Virgina Soto-Abraham, Sergio Escobar-Hernández, Diana Aguilar, Deshiré Alpizar-Rodríguez, Karen Férez-Blando, Luis Llorente
Abstract
Previous studies showed that polymerized-type I collagen (polymerized collagen) exhibits potent immunoregulatory properties. This work evaluated the effect of intramuscular administration of polymerized collagen in early and established collagen-induced arthritis (CIA) in mice and analyzed changes in Th subsets following therapy. Incidence of CIA was of 100% in mice challenged with type II collagen. Clinimorphometric analysis showed a downregulation of inflammation after administration of all treatments (P < 0.05). Histological analysis showed that the CIA-mice group had extensive bone erosion, pannus and severe focal inflammatory infiltrates. In contrast, there was a remarkable reduction in the severity of arthritis in mice under polymerized collagen, methotrexate or methotrexate/polymerized collagen treatment. Polymerized Collagen but not methotrexate induced tissue joint regeneration. Polymerized Collagen and methotrexate/polymerized collagen but not methotrexate alone induces downregulation of CD4(+)/IL17A(+) T cells and upregulation of Tregs and CD4(+)/IFN-γ(+) T cells. Thus, Polymerized Collagen could be an effective therapeutic agent in early and established rheumatoid arthritis by exerting downregulation of autoimmune inflammation.
Figures
References
- Brand DD, Latham KA, Rosloniec E. Collagen-induced arthritis. Nature Protocols. 2007;2(5):1269–1275.
- Brand DD, Kang AH, Rosloniec EF. Immunopathogenesis of collagen arthritis. Springer Seminars in Immunopathology. 2003;25(1):3–18.
- Brand DD, Kang AH, Rosloniec EF. The mouse model of collagen-induced arthritis. Methods in molecular medicine. 2004;102:295–312.
- Mauri C, Williams RO, Walmsley M, Feldmann M. Relationship between Th1/Th2 cytokine patterns and the arthritogenic response in collagen-induced arthritis. European Journal of Immunology. 1996;26(7):1511–1518.
- Doncarli A, Stasiuk LM, Fournier C, Abehsira-Amar O. Conversion in vivo from an early dominant Th0/Th1 response to a Th2 phenotype during the development of collagen-induced arthritis. European Journal of Immunology. 1997;27(6):1451–1460.
- Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annual Review of Immunology. 2007;25:821–852.
- McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nature Reviews Immunology. 2007;7(6):429–442.
- Furuzawa-Carballeda J, Vargas-Rojas MI, Cabral AR. Autoimmune inflammation from the Th17 perspective. Autoimmunity Reviews. 2007;6(3):169–175.
- Bettelli E, Oukka M, Kuchroo VK. TH-17 cells in the circle of immunity and autoimmunity. Nature Immunology. 2007;8(4):345–350.
- Fujimoto M, Serada S, Mihara M, et al. Interleukin-6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses. Arthritis & Rheumatism. 2008;58(12):3710–3719.
- Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441(7090):235–238.
- Chimal-Monroy J, Bravo-Ruiz T, Krötzsch-Gómez FE, Díaz de León L. Implantes de FibroquelMR aceleran la formación de hueso nuevo en defectos óseos inducidos experimentalmente en cráneos de rata: un estudio histológico. Revista Biomédica. 1997;8:81–88.
- Krötzsch-Gómez FE, Furuzawa-Carballeda J, Reyes-Márquez R, Quiróz- Hernández E, Díaz de León L. Cytokine expression is downregulated by collagen-polyvinylpyrrolidone in hypertrophic scars. Journal of Investigative Dermatology. 1998;111(5):828–834.
- Furuzawa-Carballeda J, Krötzsch-Gómez FE, Espinosa-Morales R, Alcalá M, Barile-Fabris L. Subcutaneous administration of collagen-polyvinylpyrrolidone down regulates IL-1β, TNF-α, TGF-β1, ELAM-1 and VCAM-1 expression in scleroderma skin lesions. Clinical and Experimental Dermatology. 2005;30(1):83–86.
- Furuzawa-Carballeda J, Alcocer-Varela J, Díaz de León L. Collagen-PVP decreases collagen turnover in synovial tissue cultures from rheumatoid arthritis patients. Annals of the New York Academy of Sciences. 1999;878:598–603.
- Furuzawa-Carballeda J, Rodríquez-Calderón R, Díaz de León L, Alcocer-Varela J. Mediators of inflammation are down-regulated while apoptosis is up-regulated in rheumatoid arthritis synovial tissue by polymerized collagen. Clinical and Experimental Immunology. 2002;130(1):140–149.
- Furuzawa-Carballeda J, Cabral AR, Zapata-Zuúñiga M, Alcocer-Varela J. Subcutaneous administration of polymerized-type I collagen for the treatment of patients with rheumatoid arthritis. An open-label pilot trial. The Journal of Rheumatology. 2003;30(2):256–259.
- Furuzawa-Carballeda J, Fenutria-Ausmequet R, Gil-Espinosa V, et al. Polymerized-type I collagen for the treatment of patients with rheumatoid arthritis. Effect of intramuscular administration in a double blind placebo-controlled clinical trial. Clinical and Experimental Rheumatology. 2006;24(5):521–528.
- Lange F, Bajtner E, Rintisch C, Nandakumar KS, Sack U, Holmdahl R. Methotrexate ameliorates T cell dependent autoimmune arthritis and encephalomyelitis but not antibody induced or fibroblast induced arthritis. Annals of the Rheumatic Diseases. 2005;64(4):599–605.
- Zhou R, Tang W, Ren Y-X, et al. (5 R)-5-Hydroxytriptolide attenuated collagen-induced arthritis in DBA/1 mice via suppressing interferon-γ production and its related signaling. The Journal of Pharmacology and Experimental Therapeutics. 2006;8(1):35–44.
- Infante-Duarte C, Horton HF, Byrne MC, Kamradt T. Microbial lipopeptides induce the production of IL-17 in Th cells. The Journal of Immunology. 2000;165(11):6107–6115.
- Chu C-Q, Swart D, Alcorn D, Tocker J, Elkon KB. Interferon-γ regulates susceptibility to collagen-induced arthritis through suppression of interleukin-17. Arthritis & Rheumatism. 2007;56(4):1145–1151.
- Manoury-Schwartz B, Chiocchia G, Bessis N, et al. High susceptibility to collagen-induced arthritis in mice lacking IFN-γ receptors. The Journal of Immunology. 1997;158(11):5504–5506.
- Vermeire K, Heremans H, Vandeputte M, Huang S, Billiau A, Matthys P. Accelerated collagen-induced arthritis in IFN-γ receptor-deficient mice. The Journal of Immunology. 1997;158(11):5507–5513.
- Kageyama Y, Koide Y, Yoshida A, et al. Reduced susceptibility to collagen-induced arthritis in mice deficient in IFN-γ/receptor. The Journal of Immunology. 1998;161(3):1542–1548.
- Bettelli E, Sullivan B, Szabo SJ, Sobel RA, Glimcher LH, Kuchroo VK. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. The Journal of Experimental Medicine. 2004;200(1):79–87.
- Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. Journal of Immunology. 2003;171(11):6173–6177.
- Lubberts E, Koenders MI, Oppers-Walgreen B, et al. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis and Rheumatism. 2004;50(2):650–659.
- Sato K, Suematsu A, Okamoto K, et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. The Journal of Experimental Medicine. 2006;203(12):2673–2682.
- Yao ZQ, Li R, Li ZG. A triple altered collagen II peptide with consecutive substitutions of TCR contacting residues inhibits collagen-induced arthritis. Annals of the Rheumatic Diseases. 2007;66(3):423–424.
- Myers LK, Sakurai Y, Rosloniec EF, Stuart JM, Kang AH. An analog peptide that suppresses collagen-induced arthritis. American Journal of the Medical Sciences. 2004;327(4):212–216.
- Sakurai Y, Brand DD, Tang B, et al. Analog peptides of type II collagen can suppress arthritis in HLA-DR4 (DRB1*0401) transgenic mice. Arthritis Research & Therapy. 2006;8(5, article R150)
- Zhao J, Li R, He J, Shi J, Long L, Zhanguo L. Mucosal administration of an altered CII263-272 peptide inhibits collagen-induced arthritis by suppression of Th1/Th17 cells and expansion of regulatory T cells. Rheumatology International. 2008;29(1):9–16.
- Segal R, Caspi D, Tishler M, Fishel B, Yaron M. Accelerated nodulosis and vasculitis during methotrexate therapy for rheumatoid arthritis. Arthritis and Rheumatism. 1988;31(9):1182–1185.
- Hessian PA, Highton J, Kean A, Sun ChK, Chin M. Cytokine profile of the rheumatoid nodule suggests that it is a Th1 granuloma. Arthritis & Rheumatism. 2003;48(2):334–338.
- Matsushita I, Uzuki M, Matsuno H, Sugiyama E, Kimura T. Rheumatoid nodulosis during methotrexate therapy in a patient with rheumatoid arthritis. Modern Rheumatology. 2006;16(6):401–403.
- Duarte J, Agua-Doce A, Oliveira VG, Fonseca JE, Graca L. Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice. PloS one. 2010;5(5):p. e10558.
- Ghosh S, Hayden MS. New regulators of NF-κB in inflammation. Nature Reviews Immunology. 2008;8(11):837–848.
Source: PubMed