Immunotherapeutic potential of collagen V oral administration in mBSA/CFA-induced arthritis
Lizandre Keren Ramos da Silveira1, Ana Paula P Velosa1, Sergio Catanozi2
1Division of Rheumatology, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Abstract:
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.
Insights
Oral collagen V (Col V) immunotherapy reduced inflammation and synovial damage in experimental arthritis. This treatment modulated the synovial matrix and showed potential for treating synovitis.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Synovial injury can expose hidden antigens, like collagen V (Col V), leading to autoantibodies and immune tolerance loss.
- This immune response contributes to joint damage in experimental arthritis models.
Purpose of the Study:
- To investigate the therapeutic effects of oral Col V administration on synovium inflammation in rats with established mBSA/CFA-induced arthritis.
- To assess Col V's impact on immune cell infiltration, extracellular matrix composition, and cytokine production.
Main Methods:
- Rats with induced arthritis received oral Col V (IA-Col V group) or saline (IA group). A control group received intra-articular saline.
- Synovial tissue and spleen cells were analyzed for inflammation markers, immune cell populations (IL-10+, FoxP3+), and extracellular matrix components (Col I, Col V).
- In vitro spleen cell stimulation with Col V assessed IL-10 production.
Main Results:
- Oral Col V significantly reduced synovial inflammation and tissue damage compared to the arthritic group.
- The IA-Col V group exhibited increased IL-10+ and FoxP3+ cells, decreased Col V, and increased Col I in the synovium.
- Spleen cells from the IA-Col V group showed enhanced IL-10 production upon in vitro Col V stimulation.
Conclusions:
- Oral collagen V administration demonstrates immunotherapeutic potential in mitigating experimental arthritis.
- This treatment modulates the synovial matrix and immune response, offering a protective effect against synovitis and joint damage.
