Abstract
The Interferon regulatory factors (IRFs) are a family of transcription factors that play pivotal roles in many aspects of the immune response, including immune cell development and differentiation and regulating responses to pathogens. Three family members, IRF3, IRF5, and IRF7, are critical to production of type I interferons downstream of pathogen recognition receptors that detect viral RNA and DNA. A fourth family member, IRF9, regulates interferon-driven gene expression. In addition, IRF4, IRF8, and IRF5 regulate myeloid cell development and phenotype, thus playing important roles in regulating inflammatory responses. Thus, understanding how their levels and activity is regulated is of critical importance given that perturbations in either can result in dysregulated immune responses and potential autoimmune disease. This review will focus the role of IRF family members in regulating type I IFN production and responses and myeloid cell development or differentiation, with particular emphasis on how regulation of their levels and activity by ubiquitination and microRNAs may impact autoimmune disease.
Highlights
This review will focus the role of Interferon regulatory factors (IRFs) family members in regulating type I IFN production and responses and myeloid cell development or differentiation, with particular emphasis on how regulation of their levels and activity by ubiquitination and microRNAs may impact autoimmune disease
Cheon et al have recently demonstrated that increased expression of STAT1 and STAT2 as a result of constitutive low level IFN-β expression gives rise to a novel transcriptional complex composed of unphosphorylated STAT1 and STAT2 complexed to IRF9 [71], which drives a subset of anti-viral genes that overlap directly with the most highly expressed IFN stimulated genes (ISGs) far identified in systemic lupus erythematosus (SLE) patients
Many of these studies were conducted in nonimmune cells, they reveal the complexity of gene expression patterns downstream of the IFN Alpha Receptor (IFNAR) receptor complex and highlight the possibility that overexpression of STAT1, STAT2, or IRF9 can have a profound effect on ISG expression and potentially allow ISG expression independent of signaling through IFNAR
Summary
Feinstein Institute for Medical Research, United States Javier Rodríguez-Carrio, Universidad de Oviedo Mieres, Spain. Specialty section: This article was submitted to Molecular Innate Immunity, a section of the journal
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