Dual specificity phosphatase 6 (DUSP6) deletion protects mice and reduces disease severity in autoimmune arthritis.

Receptor tyrosine kinases (RTK) have an important role in arthritis severity and in models of rheumatoid arthritis (RA), but their regulation is not fully understood. The dual specificity phosphatase 6 (DUSP6) has been implicated in the regulation of RTK signaling, but never in the context of arthritis and autoimmunity. We used the KRN serum induced arthritis (KSIA) model of RA and show that DUSP6-/- mice were protected and had a 50% lower maximum arthritis score (P=0.006), and reduced joint damage than C57BL/6. Serum levels of IL10 were significantly increased (>two-fold), and IL6 decreased in DUSP6-/- mice. DUSP6-/- mice had increased numbers of IL10+ cells including Tr1 regulatory cells (P< 0.01). Introduction of the IL10-/- into DUSP6-/- (double KO) reversed the DUSP6-/- protection. In conclusion, this study reports a new pro-arthritic role for DUSP6. This new discovery has the potential generate a novel target for therapies for RA and inflammatory diseases.