Dermatomyositis autoantigen CHD4 forms immune stimulatory complexes with endogenous DNA.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy belonging to the spectrum of autoimmune connective tissue diseases. DM patients present with antinuclear antibodies against Mi-2, also known as Chromodomain-helicase-DNA-binding protein 4 (CHD4). CHD4 is upregulated in DM skin biopsies and could potentially affect DM pathophysiology as it binds endogenous DNA with a high affinity (KD = 0.2 nM ± 0.076 nM) and forms CHD4-DNA complexes. The complexes are localized in the cytoplasm of UV-radiated and transfected HaCaTs and amplify the expression of interferon (IFN) regulated genes and the amount of functional CXCL10 protein stronger than DNA alone. The enhancement of the type I IFN pathway activation in HaCaTs through CHD4-DNA signalling suggests a possible mechanism for the sustainment of the pro-inflammatory vicious cycle in DM skin lesions.