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In Situ Detection of Autoreactive CD4 T Cells in Brain and Heart Using Major Histocompatibility Complex Class II Dextramers
Published on: August 1, 2014
Dermatomyositis autoantigen CHD4 forms immune stimulatory complexes with endogenous DNA
Tugce Guel1, Benedikt Scholtissek1, Julia Siegl2
1Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany.
Abstract:
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.
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