Gehrke N, Mertens C, Zillinger T et al. Oxidative Damage of DNA Confers Resistance to Cytosolic Nuclease TREX1 Degradation and Potentiates STING-Dependent Immune Sensing. Immunity (2013) Epub ahead of print. DOI: 10.1016/j.immuni.2013.08.004
Sun-oxidized cytosolic DNA is resistant to a damage-repair enzyme, and its presence triggers autoimmune inflammation in patients with lupus. This is the explanation for sun-induced lupus flares offered by a team at the University of Bonn and published in the journal Immunity.
The oxidized DNA base 8-hydroxyguanosine (8-OHG) is abundant in UV-exposed skin of lupus patients, report clinical chemist Winfried Barchet and coauthors. 8-OHG is resistant to degradation by a DNA repair enzyme known by the acronym TREX1.
Injection of DNA oxidized in this way into the skin of lupus-prone laboratory mice induced skin lesions similar to those that arise in lupus patients after sun exposure. A newly discovered immune receptor, cGAMP synthase, played a "decisive role" in the autoimmune reaction in these experiments, Barchet said in a press release, hinting at the possibility that it could inspire new treatments.