Fig. 6.

Schematic diagram of the correlation of DUSPs and ankylosing spondylitis. The mRNA levels of DUSP4, DUSP5, DUSP6, DUSP7, and DUSP14 were increased in peripheral blood T cells from ankylosing spondylitis (AS) patients, whereas the mRNA levels of DUSP22 were decreased. Downregulation of the DUSP22 protein in T cells of AS patients was concomitant to the induction of the proinflammatory cytokines TNF-α, IL-17A, and IFN-γ. DUSP22 downregulation was correlated with the values/levels of ESR, CRP, BASDAI, TNF-α, IL-17A, and IFN-γ of AS patients. Consistently, DUSP22 knockout (KO) mice spontaneously developed AS-like symptoms with induction of TNF-α, IL-17A, and IFN-γ. It is unclear whether IFN-γ contributes to the pathogenesis of AS. In addition, the mRNA levels of DUSP4, DUSP5, DUSP6, DUSP7, and DUSP14 were modestly correlated with TNF-α mRNA levels in the T cells of AS patients. The roles of DUSP4, DUSP5, DUSP6, DUSP7, and DUSP14 in the pathogenesis of AS are unclear. These findings suggest that DUSP22 downregulation in T cells plays a critical role in the pathogenesis of AS. ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index