| First Author | Laragione T | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 6 | Pages | 110158 |
| PubMed ID | 38974475 | Mgi Jnum | J:351629 |
| Mgi Id | MGI:7702965 | Doi | 10.1016/j.isci.2024.110158 |
| Citation | Laragione T, et al. (2024) DUSP6 deletion protects mice and reduces disease severity in autoimmune arthritis. iScience 27(6):110158 |
| abstractText | Receptor tyrosine kinases (RTKs) 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 showed that DUSP6(-/-) mice were protected and had a 50% lower maximum arthritis score (p = 0.006) and reduced joint damage than C57BL/6 DUSP6+/+ controls. Serum levels of interleukin (IL) 10 were significantly increased (>2-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 knockout [KO]) reversed the DUSP6(-/-) protection. In conclusion, this study reports a pro-arthritic role for DUSP6. This discovery has the potential to generate a previously unknown target for therapies for RA and inflammatory diseases. |
