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

在胶原诱导性关节炎中,聚合 I 型胶原诱导表达 Foxp3 的 CD4 调节性 T 细胞上调,并诱导产生 IL-17 的 CD4⁺ T 细胞 (Th17) 下调

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作者: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.

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