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Front. Immunol. | doi: 10.3389/fimmu.2018.02622

THERAPEUTIC TARGETING OF IRFs: PATHWAY-DEPENDENCE OR STRUCTURE-BASED?

Cherrie D. Thompson1,  Bharati Matta1 and  Betsy J. Barnes1*
  • 1Feinstein Institute for Medical Research, United States

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 signalling 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.

Keywords: IRF5, inhibition, Negative regulation, Positive regulation, Autoimmunity

Received: 04 Sep 2018; Accepted: 25 Oct 2018.

Edited by:

Hans A. Bluyssen, Adam Mickiewicz University in Poznań, Poland

Reviewed by:

Alessandra Mancino, San Raffaele Hospital (IRCCS), Italy
Tatsuma Ban, Department of Immunology, Yokohama City University Graduate School of Medicine, Japan  

Copyright: © 2018 Thompson, Matta and Barnes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Betsy J. Barnes, Feinstein Institute for Medical Research, Manhasset, New York, United States, bbarnes1@northwell.edu