35 research outputs found
Enhanced lymph node trafficking of engineered ILâ10 suppresses rheumatoid arthritis in murine models
Objective Rheumatoid arthritis (RA) is a major autoimmune disease that causes synovitis and joint damage. Although clinical trials using interleukinâ10 (ILâ10), an antiâinflammatory cytokine, have been performed as a potential treatment of RA, its therapeutic effects have been limited, potentially due to insufficient residence in lymphoid organs, where antigen recognition primarily occurs. Here, we engineered ILâ10 as a fusion with serum albumin (SA). Methods SAâfused ILâ10 was recombinantly expressed. After intravenous injection to mice, retention of SAâILâ10 at lymph node (LN), immune cell compositions at paws, and therapeutic effect on arthritis model mice were assessed. Results SA fusion to ILâ10 led to enhanced LN accumulation compared with unmodified ILâ10. Intravenous SAâILâ10 treatment restored immune cell composition in the paws to a normal status, elevated the frequency of suppressive M2 macrophages, reduced ILâ17A amount in the pawâdraining LN, and protected joint morphology. Intravenous SAâILâ10 treatment showed similar efficacy as treatment with an antiâTNFâα antibody. SAâILâ10 was equally effective when administered intravenously, locally or subcutaneously, which benefits clinical translation of this molecule. Conclusion SA fusion to ILâ10 is a simple but effective engineering strategy for RA therapy and holds clinical translational potential