α-ketoglutarate-dependent KDM6 histone demethylases regulate Interferon Stimulated Gene expression in Lupus.
Erica N MontanoMoumita BoseLihong HuoGantsetseg TumurkhuuGabriela De Los SantosBrianna SimentalAleksandr B StotlandJanet WeiC Noel Bairey MerzJo SudaGislaine MartinsSarfaraz LalaniKate LawrensonYizhou WangSarah ParkerSwamy VenuturupalliMariko IshimoriDaniel J WallaceCaroline A JefferiesPublished in: Arthritis & rheumatology (Hoboken, N.J.) (2023)
Our study suggests chronic IFNα exposure alters epigenetic regulation of ISG expression in SLE monocytes via changes in immunometabolism, a mechanism reflecting trained immunity to type I IFN. Importantly, it opens the possibility that targeting histone modifying enzymes such as KDM6A/B may reduce IFN responses in SLE.