2021年5月
Suppression of Rheumatoid Arthritis by Enhanced Lymph Node Trafficking of Engineered Interleukin‐10 in Murine Models
Arthritis & Rheumatology
- 巻
- 73
- 号
- 5
- 開始ページ
- 769
- 終了ページ
- 778
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1002/art.41585
- 出版者・発行元
- Wiley
OBJECTIVE: Rheumatoid arthritis (RA) is a major autoimmune disease that causes synovitis and joint damage. Although clinical trials have been performed using interleukin-10 (IL-10), an antiinflammatory cytokine, as a potential treatment of RA, the therapeutic effects of IL-10 have been limited, potentially due to insufficient residence in lymphoid organs, where antigen recognition primarily occurs. This study was undertaken to engineer an IL-10-serum albumin (SA) fusion protein and evaluate its effects in 2 murine models of RA. METHODS: SA-fused IL-10 (SA-IL-10) was recombinantly expressed. Mice with collagen antibody-induced arthritis (n = 4-7 per group) or collagen-induced arthritis (n = 9-15 per group) were injected intravenously with wild-type IL-10 or SA-IL-10, and the retention of SA-IL-10 in the lymph nodes (LNs), immune cell composition in the paws, and therapeutic effect of SA-IL-10 on mice with arthritis were assessed. RESULTS: SA fusion to IL-10 led to enhanced accumulation in the mouse LNs compared with unmodified IL-10. Intravenous SA-IL-10 treatment restored immune cell composition in the paws to a normal status, elevated the frequency of suppressive alternatively activated macrophages, reduced IL-17A levels in the paw-draining LN, and protected joint morphology. Intravenous SA-IL-10 treatment showed similar efficacy as treatment with an anti-tumor necrosis factor antibody. SA-IL-10 was equally effective when administered intravenously, locally, or subcutaneously, which is a benefit for clinical translation of this molecule. CONCLUSION: SA fusion to IL-10 is a simple but effective engineering strategy for RA therapy and has potential for clinical translation.
- リンク情報
-
- DOI
- https://doi.org/10.1002/art.41585
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/33169522
- URL
- https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.41585
- URL
- https://onlinelibrary.wiley.com/doi/full-xml/10.1002/art.41585
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85102177817&origin=inward
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85102177817&origin=inward
- ID情報
-
- DOI : 10.1002/art.41585
- ISSN : 2326-5191
- eISSN : 2326-5205
- PubMed ID : 33169522
- SCOPUS ID : 85102177817