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.
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.
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Colonia Sección XVI, Tlalpan, 14000 Mexico City, DF, Mexico. jfuruzawa@gmail.com
Janette
J
Furuzawa-Carballeda
Perla
P
Macip-Rodríguez
Angeles S
AS
Galindo-Feria
David
D
Cruz-Robles
Virgina
V
Soto-Abraham
Sergio
S
Escobar-Hernández
Diana
D
Aguilar
Deshiré
D
Alpizar-Rodríguez
Karen
K
Férez-Blando
Luis
L
Llorente
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D024042:Collagen Type I / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D007167:Immunotherapy; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage; D051379:Mice; D008811:Mice, Inbred DBA; D058105:Polymerization; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D015704:CD4 Antigens; D024042:Collagen Type I; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D008727:Methotrexate