Monocyte differentiation to macrophage requires interferon regulatory factor 7

Interferon regulatory factors are a growing family of transcription factor that have been implicated in cellular events such as cell-growth regulation , antiviral defense, and development of the immune system. Interferon regul atory factor 7 (IRF-7) is expressed predominantly in lymphoid tissues and h as been studied extensively in the context of viral infection and the induc tion of interferon and cytokine gene expression. In this paper, the involve ment of IRF-7 in monocyte differentiation was examined in U937, HL60, and h uman primary macrophages. We report the induction of IRF-7 expression by 12 -O-tetradecanoylphorbol-13-acetate in U937 and HL60 cells and demonstrate t hat this induction is essential for the monocyte differentiation to macroph ages. We show that the monocyte differentiation is inhibited in cells expre ssing a dominant negative IRF-7 mutant, as evidenced by decreased expressio n of two macrophage-differentiation markers, CD11b and CD11c, and impaired phagocytic activity. In addition, we demonstrate that overexpression of IRF -7 is sufficient to trigger monocyte differentiation and to induce cell cyc le arrest. The identification of IRF-7 as a key regulator in monocyte diffe rentiation suggests a novel function of IRF-7 in innate immunity.