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The family of interferon (IFN) regulatory factors exert their function in the pathogenesis of systemic lupus erythematosus (SLE) by regulating lymphocyte differentiation, inducing the production of IFN, and controlling the expression of IFN-related genes. Different interferon regulatory factors positively or negatively modulate SLE through same or different mechanisms. So it may benefit the treatment and prevention of SLE by preparation of the antagonists and/or activators of IFN regulatory factors.