Therapeutic Targeting of IRFs: Pathway-Dependence or Structure-Based?

The interferon regulatory factors (IRFs) are a family of master transcription factors that regulate pathogen-induced innate and acquired immune responses. Aberration(s) in IRF signaling pathways due to infection, genetic predisposition and/or mutation, which can lead to increased expression of type...

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Published inFrontiers in immunology Vol. 9; p. 2622
Main Authors Thompson, Cherrie D, Matta, Bharati, Barnes, Betsy J
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 20.11.2018
Subjects
autoimmunity
Immunology
inhibition
IRF5
negative regulation
positive regulation
negative regulation
inhibition
IRF5
positive regulation
autoimmunity
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Summary:The interferon regulatory factors (IRFs) are a family of master transcription factors that regulate pathogen-induced innate and acquired immune responses. Aberration(s) in IRF signaling pathways due to infection, genetic predisposition and/or mutation, which can lead to increased expression of type I interferon (IFN) genes, IFN-stimulated genes (ISGs), and other pro-inflammatory cytokines/chemokines, has been linked to the development of numerous diseases, including (but not limited to) autoimmune and cancer. What is currently lacking in the field is an understanding of how best to therapeutically target these transcription factors. Many IRFs are regulated by post-translational modifications downstream of pattern recognition receptors (PRRs) and some of these modifications lead to activation or inhibition. We and others have been able to utilize structural features of the IRFs in order to generate dominant negative mutants that inhibit function. Here, we will review potential therapeutic strategies for targeting all IRFs by using IRF5 as a candidate targeting molecule.
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This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology
Edited by: Hans A. R. Bluyssen, Adam Mickiewicz University in Poznan, Poland
Reviewed by: Tatsuma Ban, Yokohama City University Graduate School of Medicine, Japan; Alessandra Mancino, San Raffaele Hospital (IRCCS), Italy
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2018.02622