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

PLoS One. 2024 Oct 8;19(10):e0311263. doi: 10.1371/journal.pone.0311263. eCollection 2024.

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Arthritis, Experimental* / drug therapy
  • Arthritis, Experimental* / immunology
  • Arthritis, Experimental* / pathology
  • Collagen Type V* / administration & dosage
  • Collagen Type V* / immunology
  • Forkhead Transcription Factors / metabolism
  • Freund's Adjuvant / administration & dosage
  • Immunotherapy / methods
  • Interleukin-10
  • Male
  • Rats
  • Rats, Inbred Lew*
  • Serum Albumin, Bovine
  • Synovial Membrane* / immunology
  • Synovial Membrane* / pathology

Substances

  • Collagen Type V
  • Freund's Adjuvant
  • methylated bovine serum albumin
  • Interleukin-10
  • Forkhead Transcription Factors
  • Foxp3 protein, rat
  • Serum Albumin, Bovine

Grants and funding

“This work was supported by grants from the São Paulo Research Foundation - FAPESP [2019/24178-0] for the Silveira LKR, FAPESP [2018/20403-6 and 2023/02755-0] for Capelozzi, VL and Baldavira CM, FAPESP [2021/13220-5] for Velosa AP and from CNPq - National Council for Scientific and Technological Development [303735/2021-0] for Capelozzi, VL. The FAPESP is a public institution that promotes academic research of the government of the state of São Paulo, Brazil. The CNPq is an organization linked to the Ministry of Science, Technology and Innovation to encourage research in Brazil. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript”.