Interferon regulatory factor 5 is aprotein that in humans is encoded by theIRF5gene.[5] The IRF family is a group of transcription factors that are involved in signaling for virus responses in mammals along with regulation of certain cellular functions.[6]
IRF5 is a member of theinterferon regulatory factor (IRF) family, a group oftranscription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conservedN-terminalDNA-binding domain containingtryptophan (W) repeats. Alternative splice variants encoding different isoforms exist.[5] The regulatory and repression regions of the IRF family are mainly located in theC-terminal of the IRF.[7]
A 2020 study showed that an adaptor protein named TASL play an important regulatory role in IRF5 activation by being phosphorylated at the pLxIS motif,[8] drawing a similar analogy to theIRF3 activation pathway through the adaptor proteinsMAVS,STING andTRIF.[9]
IRF5 acts as a molecular switch that controls whethermacrophages will promote or inhibit inflammation. Blocking the production of IRF5 in macrophages may help treat a wide range of autoimmune diseases, and that boosting IRF5 levels might help treat people whose immune systems are weak, compromised, or damaged. IRF5 seems to work "either by interacting with DNA directly, or by interacting with other proteins that themselves control which genes are switched on."[10]
The IRF family regulates the gene expression for theinterferon (IFN) response to viral infections.[6] IRF5 is a direct transducer to interferon signaling and is activated via phosphorylation.[11] The IRF family can also initiate theJAK/STAT signaling pathway by binding to transmembrane receptors that activate JAK.[12] IRFs, IFNs, and the JAK/STAT signaling pathway work together to fight viral infections in mammals through specific signals.[13]
^Chistiakov DA, Myasoedova VA, Revin VV, Orekhov AN, Bobryshev YV (January 2018). "The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2".Immunobiology.223 (1):101–111.doi:10.1016/j.imbio.2017.10.005.PMID29032836.
^Barnes B, Lubyova B, Pitha PM (January 2002). "On the role of IRF in host defense".Journal of Interferon & Cytokine Research.22 (1):59–71.doi:10.1089/107999002753452665.PMID11846976.
Barnes B, Lubyova B, Pitha PM (January 2002). "On the role of IRF in host defense".Journal of Interferon & Cytokine Research.22 (1):59–71.doi:10.1089/107999002753452665.PMID11846976.
Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW, et al. (May 2006). "A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus".Nature Genetics.38 (5):550–555.doi:10.1038/ng1782.PMID16642019.S2CID21426281.
