Immunotherapeutic potential of collagen V oral administration in mBSA/CFA-induced arthritis

by Lizandre Keren Ramos da Silveira, Ana Paula P. Velosa, Sergio Catanozi, Marco Aurélio A. Pereira, Antonio dos Santos Filho, Fabio Luiz N. Marques, Daniele de Paula Faria, Caroline Cristiano Real, Sandra de M. Fernezlian, Amanda Flores Yanke, Zelita Aparecida de J. Queiroz, Vitória Elias Contini, Thays de Matos Lobo, Solange Carrasco, Camila Machado Baldavira, Cláudia Goldenstein-Schainberg, Ricardo Fuller, Vera L. Capelozzi, Walcy R. Teodoro

We hypothesized that after synovial injury, collagen V (Col V) expose occult antigens, and Col V autoantibodies develop, indicating the loss of immune tolerance against this molecule, thus leading to damage to mesenchymal-derived cells as well as the extracellular matrix in experimental arthritis. Thus, the present study investigated the effects of oral administration of Col V on the synovium after the development of inflammation in mBSA/CFA-induced arthritis. After fourteen days of intraarticular administration of mBSA, 10 male Lewis rats were orally administered Col V (500 μg/300 μL) diluted in 0.01 N acetic acid (IA-Col V group). The arthritic group (IA group, n = 10) received only intraarticular mBSA. An intra-articular saline injection (20 μL) was given to the control group (CT-Col V, n = 5). IA group presented damaged synovia, the expansion of the extracellular matrix by cellular infiltrate, which was characterized by T and B lymphocytes, and fibroblastic infiltration. In contrast, after Col V oral immunotherapy IA-Col V group showed a significant reduction in synovial inflammation and intense expression of IL-10+ and FoxP3+ cells, in addition to a reduction in Col V and an increase in Col I in the synovia compared to those in the IA group. Furthermore, an increase in IL-10 production was detected after IA-Col V group spleen cell stimulation with Col V in vitro. PET imaging did not differ between the groups. The evaluation of oral treatment with Col V, after mBSA/CFA-induced arthritis in rats, protects against inflammation and reduces synovial tissue damage, through modulation of the synovial matrix, showing an immunotherapeutic potential in inhibiting synovitis.