Suppression of Rheumatoid Arthritis by Enhanced Lymph Node Trafficking of Engineered Interleukin-10 in Murine Models

Arthritis Rheumatol. 2021 May;73(5):769-778. doi: 10.1002/art.41585. Epub 2021 Mar 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / metabolism
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / metabolism
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Disease Models, Animal
  • Foot
  • Foot Joints / drug effects*
  • Foot Joints / immunology
  • Foot Joints / metabolism
  • Foot Joints / pathology
  • Hindlimb
  • Histocompatibility Antigens Class I / metabolism
  • Injections, Intravenous
  • Interleukin-10 / pharmacology*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Interleukin-6 / immunology
  • Lymph Nodes / immunology*
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Protein Engineering
  • Protein Transport
  • Receptors, Fc / metabolism
  • Recombinant Fusion Proteins / pharmacology*
  • Serum Albumin / pharmacology*
  • Transforming Growth Factor beta / drug effects
  • Transforming Growth Factor beta / immunology
  • Tumor Necrosis Factor Inhibitors / pharmacology


  • Histocompatibility Antigens Class I
  • Il17a protein, mouse
  • Interleukin-17
  • Interleukin-6
  • Receptors, Fc
  • Recombinant Fusion Proteins
  • Serum Albumin
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor Inhibitors
  • Interleukin-10
  • Fc receptor, neonatal