Abstract
Transcription factors of the interferon regulatory factor (IRF) family commands the entire type I interferon (IFN) system from induction of IFNs to diverse IFN responses, thereby providing a principal basis for host resistance against pathogens. However, the family has various additional roles. Regulating the development of the immune system, IRFs shape the establishment and execution of innate and adaptive immunity. IRFs also regulate growth and differentiation of many cell types, thus playing a role in leukemia and other cancers. In addition, evidence indicates that IRFs confer antiviral mechanisms not directly ascribed to the IFN system. This review deals with the diverse roles of IRFs in host defense and discusses the molecular mechanisms by which they regulate target gene transcription.
Highlights
In the past a few years much advancement has been made on the function of interferon regulatory factor (IRF),2 signaling pathways that lead to innate immunity, their roles in growth and development, and their structures
Among nine mammalian IRFs, IRF-3 and IRF-7 are early IRFs activated by Toll-like receptor (TLR)2 and other types of signaling that play a pivotal role in the initial induction of type I IFNs
Besides regulating the IFN system, the IRF family participates in directing the development of innate and adaptive immunity, a role best illustrated by the activity of IRF-4 and IRF-8
Summary
Among nine mammalian IRFs, IRF-3 and IRF-7 are early IRFs activated by Toll-like receptor (TLR) and other types of signaling that play a pivotal role in the initial induction of type I IFNs. In addition to IFN induction, IRFs direct the entire type I IFN responsive-. Following IFN-receptor interaction, a latent cytoplasmic IRF-9 complexes with Stat and Stat through the activation of the JAK/STAT pathway, binds to the IFN-stimulated response element (ISRE), and stimulates transcription of a large set of IFNstimulated genes (see Ref. 3 for review). In addition to the above noted IRFs, other family members modulate the extent and modes of IFN induction as well as IFN responses in subsequent steps. IFNs are produced in dendritic cells (DCs) at much higher levels than in other cells. This is in part achieved by the activity of IRF-8 [5, 6]
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