142: Therapeutic peptides from IK cytokine ameliorate rheumatoid arthritis through the suppression of macrophage activation as well as TH and TH7 cell differentiation

Abstract

The pathogenesis of inflammatory autoimmune rheumatoid arthritis (RA) is driven by the activation of macrophages and the development of pathogenic interferon-g (IFN-g)- and interleukin-17 (IL-17)-producing CD4 + T cells (T H 1 and T H 17 cells). Here, we found that truncated IK (tIK) cytokine, an inhibitor of IFN-g-induced MHC class II expression, ameliorated RA in a mouse model and was associated with decreases in joint swelling, bone destruction, and incidence of RA. Notably, the potential phosphorylation sites on tIK cytokine were identified. Interestingly, tIK active peptides showed an immune regulatory function through inhibition of pathogenic macrophage activation and suppression of T H 1 and T H 17 cell differentiation. Moreover, in a mouse model of RA, administration of tIK active peptides potently suppressed the progression of inflammatory arthritis, and this suppression correlated significantly with reduced incidence and severity of arthritis. These findings suggest that tIK cytokine may be an effective immunotherapeutic approach for RA through its immune-regulating actions.