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,Luis Llorente,Angeles S Galindo-Feria,Karen Férez-Blando,Perla Macip-Rodríguez,Virgina Soto-Abraham,Diana Aguilar,Sergio Escobar-Hernández,Deshiré Alpizar-Rodríguez,David Cruz-Robles

doi:10.1155/2012/618608

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.

Highlights

Rheumatoid arthritis (RA) is a common systemic disorder characterized by autoimmunity and chronic inflammation of multiple joints
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 Collagen-induced arthritis (CIA)
We show that Polymerized Collagen suppresses the development of CIA by enhancing a proportion of Treg cells while simultaneously diminishing Th17 cells suggesting that Polymerized Collagen ameliorates autoimmune arthritis through the regulation of both Treg/Th17 differentiation and Th1/Th2 balance

Summary

Introduction

Rheumatoid arthritis (RA) is a common systemic disorder characterized by autoimmunity and chronic inflammation of multiple joints. CIA is induced in genetically susceptible strains of mice by immunization with type II bovine collagen (CII). This study focuses on the effect of polymerized-type I collagen on Th subsets and its primary mechanism of action in early and established CIA in mice. One percent Polymerized Collagen addition to synovial tissue cultures from non-RA and RA cultures does not induce any change in DNA concentration or metabolism. Polymerized Collagen induces the recovery of type III collagen at similar levels to those detected in normal synovial tissue. We show that Polymerized Collagen suppresses the development of CIA by enhancing a proportion of Treg cells while simultaneously diminishing Th17 cells suggesting that Polymerized Collagen ameliorates autoimmune arthritis through the regulation of both Treg/Th17 differentiation and Th1/Th2 balance

Materials and Methods

Disease Models

Results

Discussion