Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2012, Article ID 618608, 11 pages doi:10.1155/2012/618608 Research Article 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, 1 Perla Macip-Rodr´ ıguez, 1 Angeles S. Galindo-Feria, 1 David Cruz-Robles, 2 Virgina Soto-Abraham, 2 Sergio Escobar-Hern´ andez, 2 Diana Aguilar, 3 Deshir´ e Alpizar-Rodr´ ıguez, 1 Karen F´ erez-Blando, 1 and Luis Llorente 1 1 Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M´ edicas y Nutrici´ on Salvador Zubir´ an, Vasco de Quiroga No. 15, Colonia Secci´ on XVI, Tlalpan, 14000 Mexico City, DF, Mexico 2 Department of Pathology, Instituto Nacional de Cardiolog´ ıa Ignacio Ch´ avez, Juan Badiano No. 1, Colonia Secci´ on XVI, Tlalpan, 14080 Mexico City, DF, Mexico 3 Department of Experimental Pathology, Instituto Nacional de Ciencias M´ edicas y Nutrici´ on Salvador Zubir´ an, Vasco de Quiroga No. 15, Colonia Secci´ on XVI, Tlalpan, 14000 Mexico City, DF, Mexico Correspondence should be addressed to Janette Furuzawa-Carballeda, jfuruzawa@gmail.com Received 13 June 2011; Revised 22 July 2011; Accepted 23 July 2011 Academic Editor: Zoltan Szekanecz Copyright © 2012 Janette Furuzawa-Carballeda et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. 1. Introduction Rheumatoid arthritis (RA) is a common systemic disorder characterized by autoimmunity and chronic inflammation of multiple joints. Collagen-induced arthritis (CIA) is a well-established animal model of RA [1]. CIA is induced in genetically susceptible strains of mice by immunization with type II bovine collagen (CII). Although the effector mechanisms of inflammation ultimately result in pathogenic lesions of joints (inflammatory component of CIA), there is considerable evidence implicating CII-specific CD4 + T cells as primary mediators of disease induction (T-cell immunity component of CIA) [2, 3]. After antigenic stimulation naive CD4 + T cells develop into different types of helper T cells, each produces its own set of cytokines that mediate different responses in CIA. It has been well documented that Th1 cells produce interferon (IFN)-γ and interleukin (IL)-2 and have been considered to be the major mediator of the disease [4, 5]. However, the notion that CIA is a Th1-mediated disorder has been challenged by studies using