Transcriptional control of metabolism by interferon regulatory factors.

Miyamoto, M. et al. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-β gene regulatory elements. Cell 54, 903–913 (1988).

pubmed: 3409321 doi: 10.1016/S0092-8674(88)91307-4

Nehyba, J., Hrdlickova, R. & Bose, H. R. Dynamic evolution of immune system regulators: the history of the interferon regulatory factor family. Mol. Biol. Evol. 26, 2539–2550 (2009).

pubmed: 19638535 pmcid: 2767096 doi: 10.1093/molbev/msp167

Tanaka, N., Kawakami, T. & Taniguchi, T. Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system. Mol. Cell Biol. 13, 4531–4538 (1993).

pubmed: 7687740 pmcid: 360068

Taniguchi, T., Ogasawara, K., Takaoka, A. & Tanaka, N. IRF family of transcription factors as regulators of host defense. Annu. Rev. Immunol. 19, 623–655 (2001).

pubmed: 11244049 doi: 10.1146/annurev.immunol.19.1.623

Chen, W. & Royer, W. E. Jr. Structural insights into interferon regulatory factor activation. Cell Signal. 22, 883–887 (2010).

pubmed: 20043992 doi: 10.1016/j.cellsig.2009.12.005

Negishi, H., Taniguchi, T. & Yanai, H. The interferon (IFN) class of cytokines and the IFN regulatory factor (IRF) transcription factor family. Cold Spring Harb. Perspect. Biol. 10, a028423 (2018).

pubmed: 28963109 pmcid: 6211389 doi: 10.1101/cshperspect.a028423

Zhao, G. N., Jiang, D. S. & Li, H. Interferon regulatory factors: at the crossroads of immunity, metabolism, and disease. Biochim. Biophys. Acta 1852, 365–378 (2015).

pubmed: 24807060 doi: 10.1016/j.bbadis.2014.04.030

Jefferies, C. A. Regulating IRFs in IFN driven disease. Front. Immunol. 10, 325 (2019).

pubmed: 30984161 pmcid: 6449421 doi: 10.3389/fimmu.2019.00325

Mogensen, T. H. IRF and STAT transcription factors — from basic biology to roles in infection, protective immunity, and primary immunodeficiencies. Front. Immunol. 9, 3047 (2018).

pubmed: 30671054 doi: 10.3389/fimmu.2018.03047

Yanai, H., Negishi, H. & Taniguchi, T. The IRF family of transcription factors: inception, impact and implications in oncogenesis. Oncoimmunology 1, 1376–1386 (2012).

pubmed: 23243601 pmcid: 3518510 doi: 10.4161/onci.22475

Yu, L., Wang, L. & Chen, S. Endogenous Toll-like receptor ligands and their biological significance. J. Cell Mol. Med. 14, 2592–2603 (2010).

pubmed: 20629986 pmcid: 4373479 doi: 10.1111/j.1582-4934.2010.01127.x

Alexopoulou, L., Holt, A. C., Medzhitov, R. & Flavell, R. A. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413, 732–738 (2001).

pubmed: 11607032 doi: 10.1038/35099560

Kariko, K., Ni, H., Capodici, J., Lamphier, M. & Weissman, D. mRNA is an endogenous ligand for Toll-like receptor 3. J. Biol. Chem. 279, 12542–12550 (2004).

pubmed: 14729660 doi: 10.1074/jbc.M310175200

Bernard, J. J. et al. Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nat. Med. 18, 1286–1290 (2012).

pubmed: 22772463 doi: 10.1038/nm.2861

Lu, Y. C., Yeh, W. C. & Ohashi, P. S. LPS/TLR4 signal transduction pathway. Cytokine 42, 145–151 (2008).

pubmed: 18304834 doi: 10.1016/j.cyto.2008.01.006

Termeer, C. et al. Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4. J. Exp. Med. 195, 99–111 (2002).

pubmed: 11781369 pmcid: 2196009 doi: 10.1084/jem.20001858

Lotze, M. T. & Tracey, K. J. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat. Rev. Immunol. 5, 331–342 (2005).

pubmed: 15803152 doi: 10.1038/nri1594

Ohashi, K., Burkart, V., Flohé, S. & Kolb, H. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J. Immunol. 164, 558–561 (2000).

pubmed: 10623794 doi: 10.4049/jimmunol.164.2.558

Roelofs, M. F. et al. Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis. J. Immunol. 176, 7021–7027 (2006).

pubmed: 16709864 doi: 10.4049/jimmunol.176.11.7021

Asea, A. et al. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem. 277, 15028–15034 (2002).

pubmed: 11836257 doi: 10.1074/jbc.M200497200

Shi, H. et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116, 3015–3025 (2006).

pubmed: 17053832 pmcid: 1616196 doi: 10.1172/JCI28898

Mukhopadhyay, S. & Bhattacharya, S. Plasma fetuin-a triggers inflammatory changes in macrophages and adipocytes by acting as an adaptor protein between NEFA and TLR-4. Diabetologia 59, 859–860 (2016).

pubmed: 26781474 doi: 10.1007/s00125-016-3866-y

Yang, Y. et al. The emerging role of Toll-like receptor 4 in myocardial inflammation. Cell Death Dis. 7, e2234 (2016).

pubmed: 27228349 pmcid: 4917669 doi: 10.1038/cddis.2016.140

Kim, J. J. & Sears, D. D. TLR4 and insulin resistance. Gastroenterol. Res. Pract. 2010, 212563 (2010).

pubmed: 20814545 pmcid: 2931384 doi: 10.1155/2010/212563

Honda, K. & Taniguchi, T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat. Rev. Immunol. 6, 644–658 (2006).

pubmed: 16932750 doi: 10.1038/nri1900

Kawai, T. & Akira, S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11, 373–384 (2010).

pubmed: 20404851 doi: 10.1038/ni.1863

Wang, L., Li, D., Yang, K., Hu, Y. & Zeng, Q. Toll-like receptor-4 and mitogen-activated protein kinase signal system are involved in activation of dendritic cells in patients with acute coronary syndrome. Immunology 125, 122–130 (2008).

pubmed: 18373609 pmcid: 2526266 doi: 10.1111/j.1365-2567.2008.02827.x

Weighardt, H. et al. Identification of a TLR4- and TRIF-dependent activation program of dendritic cells. Eur. J. Immunol. 34, 558–564 (2004).

pubmed: 14768061 doi: 10.1002/eji.200324714

Fitzgerald, K. A. et al. IKKε and TBK1 are essential components of the IRF3 signaling pathway. Nat. Immunol. 4, 491–496 (2003).

pubmed: 12692549 doi: 10.1038/ni921

Qin, B. Y. et al. Crystal structure of IRF-3 in complex with CBP. Structure 13, 1269–1277 (2005).

pubmed: 16154084 doi: 10.1016/j.str.2005.06.011

Grandvaux, N. et al. Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genes. J. Virol. 76, 5532–5539 (2002).

pubmed: 11991981 pmcid: 137057 doi: 10.1128/JVI.76.11.5532-5539.2002

Kumar, K. P., McBride, K. M., Weaver, B. K., Dingwall, C. & Reich, N. C. Regulated nuclear-cytoplasmic localization of interferon regulatory factor 3, a subunit of double-stranded RNA-activated factor 1. Mol. Cell. Biol. 20, 4159–4168 (2000).

pubmed: 10805757 pmcid: 85785 doi: 10.1128/MCB.20.11.4159-4168.2000

Hiscott, J. et al. Triggering the interferon response: the role of IRF-3 transcription factor. J. Interferon Cytokine Res. 19, 1–13 (1999).

pubmed: 10048763 doi: 10.1089/107999099314360

Doyle, S. E. et al. IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity 17, 251–263 (2002).

pubmed: 12354379 doi: 10.1016/S1074-7613(02)00390-4

Panne, D., Maniatis, T. & Harrison, S. C. An atomic model of the interferon-β enhanceosome. Cell 129, 1111–1123 (2007).

pubmed: 17574024 pmcid: 2020837 doi: 10.1016/j.cell.2007.05.019

Yoneyama, M. et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 5, 730–737 (2004).

pubmed: 15208624 doi: 10.1038/ni1087

Yoneyama, M. et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J. Immunol. 175, 2851–2858 (2005).

pubmed: 16116171 doi: 10.4049/jimmunol.175.5.2851

Tengroth, L. et al. Functional effects of Toll-like receptor (TLR)3, 7, 9, RIG-I and MDA-5 stimulation in nasal epithelial cells. PLoS One 9, e98239 (2014).

pubmed: 24886842 pmcid: 4041746 doi: 10.1371/journal.pone.0098239

Yoneyama, M. & Fujita, T. RNA recognition and signal transduction by RIG-I-like receptors. Immunol. Rev. 227, 54–65 (2009).

pubmed: 19120475 doi: 10.1111/j.1600-065X.2008.00727.x

Dixit, E. et al. Peroxisomes are signaling platforms for antiviral innate immunity. Cell 141, 668–681 (2010).

pubmed: 20451243 pmcid: 3670185 doi: 10.1016/j.cell.2010.04.018

Liu, X. Y., Chen, W., Wei, B., Shan, Y. F. & Wang, C. IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1. J. Immunol. 187, 2559–2568 (2011).

pubmed: 21813773 doi: 10.4049/jimmunol.1100963

Kato, H. et al. Cell type-specific involvement of RIG-I in antiviral response. Immunity 23, 19–28 (2005).

pubmed: 16039576 doi: 10.1016/j.immuni.2005.04.010

Sun, L., Wu, J., Du, F., Chen, X. & Chen, Z. J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339, 786–791 (2013).

pubmed: 23258413 doi: 10.1126/science.1232458

Wu, X. et al. Molecular evolutionary and structural analysis of the cytosolic DNA sensor cGAS and STING. Nucleic Acids Res. 42, 8243–8257 (2014).

pubmed: 24981511 pmcid: 4117786 doi: 10.1093/nar/gku569

Li, T. & Chen, Z. J. The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer. J. Exp. Med. 215, 1287–1299 (2018).

pubmed: 29622565 pmcid: 5940270 doi: 10.1084/jem.20180139

Chen, Q., Sun, L. & Chen, Z. J. Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat. Immunol. 17, 1142–1149 (2016).

pubmed: 27648547 doi: 10.1038/ni.3558

White, M. J. et al. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell 159, 1549–1562 (2014).

pubmed: 25525874 pmcid: 4520319 doi: 10.1016/j.cell.2014.11.036

West, A. P. et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520, 553–557 (2015).

pubmed: 25642965 pmcid: 4409480 doi: 10.1038/nature14156

Wu, J. et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339, 826–830 (2013).

pubmed: 23258412 doi: 10.1126/science.1229963

Reilly, S. M. et al. An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice. Nat. Med. 19, 313–321 (2013).

pubmed: 23396211 pmcid: 3594079 doi: 10.1038/nm.3082

Zhao, P. et al. TBK1 at the crossroads of inflammation and energy homeostasis in adipose tissue. Cell 172, 731–743.e12 (2018).

pubmed: 29425491 pmcid: 5808582 doi: 10.1016/j.cell.2018.01.007

Hrincius, E. R. et al. Phosphatidylinositol-3-kinase (PI3K) is activated by influenza virus vRNA via the pathogen pattern receptor Rig-I to promote efficient type I interferon production. Cell Microbiol. 13, 1907–1919 (2011).

pubmed: 21899695 doi: 10.1111/j.1462-5822.2011.01680.x

Joung, S. M. et al. Akt contributes to activation of the TRIF-dependent signaling pathways of TLRs by interacting with TANK-binding kinase 1. J. Immunol. 186, 499–507 (2011).

pubmed: 21106850 doi: 10.4049/jimmunol.0903534

Sarkar, S. N. et al. Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling. Nat. Struct. Mol. Biol. 11, 1060–1067 (2004).

pubmed: 15502848 doi: 10.1038/nsmb847

Yeon, S. H., Song, M. J., Kang, H. R. & Lee, J. Y. Phosphatidylinositol-3-kinase and Akt are required for RIG-I-mediated anti-viral signalling through cross-talk with IPS-1. Immunology 144, 312–320 (2015).

pubmed: 25158146 pmcid: 4298425 doi: 10.1111/imm.12373

Ren, D. et al. Metformin activates the STING/IRF3/IFN-β pathway by inhibiting AKT phosphorylation in pancreatic cancer. Am. J. Cancer Res. 10, 2851–2864 (2020).

pubmed: 33042621 pmcid: 7539786

Xiao, J. et al. Targeting 7-dehydrocholesterol reductase integrates cholesterol metabolism and IRF3 activation to eliminate infection. Immunity 52, 109–122.e6 (2020).

pubmed: 31882361 doi: 10.1016/j.immuni.2019.11.015

Bluher, M. et al. Activated Ask1-MKK4-p38MAPK/JNK stress signaling pathway in human omental fat tissue may link macrophage infiltration to whole-body Insulin sensitivity. J. Clin. Endocrinol. Metab. 94, 2507–2515 (2009).

pubmed: 19351724 doi: 10.1210/jc.2009-0002

Lucchini, F. C. et al. ASK1 inhibits browning of white adipose tissue in obesity. Nat. Commun. 11, 1642 (2020).

pubmed: 32242025 pmcid: 7118089 doi: 10.1038/s41467-020-15483-7

Yang, S. et al. Metabolic enzyme UAP1 mediates IRF3 pyrophosphorylation to facilitate innate immune response. Mol. Cell 83, 298–313.e8 (2023).

pubmed: 36603579 doi: 10.1016/j.molcel.2022.12.007

Tian, M. et al. IRF3 prevents colorectal tumorigenesis via inhibiting the nuclear translocation of β-catenin. Nat. Commun. 11, 5762 (2020).

pubmed: 33188184 pmcid: 7666182 doi: 10.1038/s41467-020-19627-7

Chattopadhyay, S., Kuzmanovic, T., Zhang, Y., Wetzel, J. L. & Sen, G. C. Ubiquitination of the transcription factor IRF-3 activates RIPA, the apoptotic pathway that protects mice from viral pathogenesis. Immunity 44, 1151–1161 (2016).

pubmed: 27178468 pmcid: 4991351 doi: 10.1016/j.immuni.2016.04.009

Sanz-Garcia, C. et al. The non-transcriptional activity of IRF3 modulates hepatic immune cell populations in acute-on-chronic ethanol administration in mice. J. Hepatol. 70, 974–984 (2019).

pubmed: 30710579 pmcid: 6462245 doi: 10.1016/j.jhep.2019.01.021

Xu, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112, 1821–1830 (2003).

pubmed: 14679177 pmcid: 296998 doi: 10.1172/JCI200319451

Weisberg, S. P. et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796–1808 (2003).

pubmed: 14679176 pmcid: 296995 doi: 10.1172/JCI200319246

Kawai, T., Autieri, M. V. & Scalia, R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am. J. Physiol. Cell Physiol. 320, C375–C391 (2021).

pubmed: 33356944 doi: 10.1152/ajpcell.00379.2020

Rohm, T. V., Meier, D. T., Olefsky, J. M. & Donath, M. Y. Inflammation in obesity, diabetes, and related disorders. Immunity 55, 31–55 (2022).

pubmed: 35021057 pmcid: 8773457 doi: 10.1016/j.immuni.2021.12.013

Cani, P. D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761–1772 (2007).

pubmed: 17456850 doi: 10.2337/db06-1491

Erridge, C., Attina, T., Spickett, C. M. & Webb, D. J. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am. J. Clin. Nutr. 86, 1286–1292 (2007).

pubmed: 17991637 doi: 10.1093/ajcn/86.5.1286

Vetrani, C. et al. From gut microbiota through low-grade inflammation to obesity: key players and potential targets. Nutrients 14, 2103 (2022).

pubmed: 35631244 pmcid: 9145366 doi: 10.3390/nu14102103

Kim, F. et al. Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity. Circ. Res. 100, 1589–1596 (2007).

pubmed: 17478729 doi: 10.1161/CIRCRESAHA.106.142851

Poggi, M. et al. C3H/HeJ mice carrying a Toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet. Diabetologia 50, 1267–1276 (2007).

pubmed: 17426960 doi: 10.1007/s00125-007-0654-8

Suganami, T. et al. Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation. Biochem. Biophys. Res. Commun. 354, 45–49 (2007).

pubmed: 17210129 doi: 10.1016/j.bbrc.2006.12.190

Tsukumo, D. M. et al. Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 56, 1986–1998 (2007).

pubmed: 17519423 doi: 10.2337/db06-1595

Yuzefovych, L. V. et al. Plasma mitochondrial DNA is elevated in obese type 2 diabetes mellitus patients and correlates positively with insulin resistance. PLoS One 14, e0222278 (2019).

pubmed: 31600210 pmcid: 6786592 doi: 10.1371/journal.pone.0222278

Alkhouri, N. et al. Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J. Biol. Chem. 285, 3428–3438 (2010).

pubmed: 19940134 doi: 10.1074/jbc.M109.074252

Ballak, D. B. et al. TLR-3 is present in human adipocytes, but its signalling is not required for obesity-induced inflammation in adipose tissue in vivo. PLoS One 10, e0123152 (2015).

pubmed: 25867514 pmcid: 4395029 doi: 10.1371/journal.pone.0123152

Nance, S. A., Muir, L. & Lumeng, C. Adipose tissue macrophages: regulators of adipose tissue immunometabolism during obesity. Mol. Metab. 66, 101642 (2022).

pubmed: 36402403 pmcid: 9703629 doi: 10.1016/j.molmet.2022.101642

Chavakis, T., Alexaki, V. I. & Ferrante, A. W. Jr Macrophage function in adipose tissue homeostasis and metabolic inflammation. Nat. Immunol. 24, 757–766 (2023).

pubmed: 37012544 doi: 10.1038/s41590-023-01479-0

Chistiakov, D. A., Myasoedova, V. A., Revin, V. V., Orekhov, A. N. & Bobryshev, Y. V. The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2. Immunobiology 223, 101–111 (2018).

pubmed: 29032836 doi: 10.1016/j.imbio.2017.10.005

Chechushkov, A. V. et al. Effect of oxidized dextran on cytokine production and activation of IRF3 transcription factor in macrophages from mice of opposite strains with different sensitivity to tuberculosis infection. Bull. Exp. Biol. Med. 164, 738–742 (2018).

pubmed: 29658082 doi: 10.1007/s10517-018-4070-5

Yanai, H. et al. Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice. Proc. Natl Acad. Sci. USA 115, 5253–5258 (2018).

pubmed: 29712834 pmcid: 5960330 doi: 10.1073/pnas.1803936115

Kuroda, M. et al. Interferon regulatory factor 7 mediates obesity-associated MCP-1 transcription. PLoS One 15, e0233390 (2020).

pubmed: 32437400 pmcid: 7241760 doi: 10.1371/journal.pone.0233390

Kanda, H. et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J. Clin. Invest. 116, 1494–1505 (2006).

pubmed: 16691291 pmcid: 1459069 doi: 10.1172/JCI26498

Takahashi, K. et al. Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. J. Biol. Chem. 278, 46654–46660 (2003).

pubmed: 13129912 doi: 10.1074/jbc.M309895200

Kamei, N. et al. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J. Biol. Chem. 281, 26602–26614 (2006).

pubmed: 16809344 doi: 10.1074/jbc.M601284200

Sartipy, P. & Loskutoff, D. J. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc. Natl Acad. Sci. USA 100, 7265–7270 (2003).

pubmed: 12756299 pmcid: 165864 doi: 10.1073/pnas.1133870100

Kumari, M. et al. IRF3 promotes adipose inflammation and insulin resistance and represses browning. J. Clin. Invest. 126, 2839–2854 (2016).

pubmed: 27400129 pmcid: 4966307 doi: 10.1172/JCI86080

Yan, S. et al. IRF3 reduces adipose thermogenesis via ISG15-mediated reprogramming of glycolysis. J. Clin. Invest. 131, e144888 (2021).

pubmed: 33571167 pmcid: 8011904 doi: 10.1172/JCI144888

Mikkelsen, T. S. et al. Comparative epigenomic analysis of murine and human adipogenesis. Cell 143, 156–169 (2010).

pubmed: 20887899 pmcid: 2950833 doi: 10.1016/j.cell.2010.09.006

Eguchi, J. et al. Interferon regulatory factors are transcriptional regulators of adipogenesis. Cell Metab. 7, 86–94 (2008).

pubmed: 18177728 pmcid: 2278019 doi: 10.1016/j.cmet.2007.11.002

Tang, P. et al. Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3. Cell Death Differ. 28, 3022–3035 (2021).

pubmed: 34091599 pmcid: 8563729 doi: 10.1038/s41418-021-00798-9

Chow, E. K. et al. A role for IRF3-dependent RXRα repression in hepatotoxicity associated with viral infections. J. Exp. Med. 203, 2589–2602 (2006).

pubmed: 17074929 pmcid: 2118146 doi: 10.1084/jem.20060929

Cohen, P. & Kajimura, S. The cellular and functional complexity of thermogenic fat. Nat. Rev. Mol. Cell Biol. 22, 393–409 (2021).

pubmed: 33758402 pmcid: 8159882 doi: 10.1038/s41580-021-00350-0

Dulloo, A. G. & Montani, J. P. Body composition, inflammation and thermogenesis in pathways to obesity and the metabolic syndrome: an overview. Obes. Rev. 13, 1–5 (2012).

pubmed: 23107254 doi: 10.1111/j.1467-789X.2012.01032.x

Goto, T. et al. Proinflammatory cytokine interleukin-1β suppresses cold-induced thermogenesis in adipocytes. Cytokine 77, 107–114 (2016).

pubmed: 26556104 doi: 10.1016/j.cyto.2015.11.001

Sakamoto, T. et al. Inflammation induced by RAW macrophages suppresses UCP1 mRNA induction via ERK activation in 10T1/2 adipocytes. Am. J. Physiol. Cell Physiol. 304, C729–C738 (2013).

pubmed: 23302779 pmcid: 3625802 doi: 10.1152/ajpcell.00312.2012

Sakamoto, T. et al. Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice. Am. J. Physiol. Endocrinol. Metab. 310, E676–E687 (2016).

pubmed: 26884382 doi: 10.1152/ajpendo.00028.2015

Nisoli, E. et al. Tumor necrosis factor α mediates apoptosis of brown adipocytes and defective brown adipocyte function in obesity. Proc. Natl Acad. Sci. USA 97, 8033–8038 (2000).

pubmed: 10884431 pmcid: 16665 doi: 10.1073/pnas.97.14.8033

Chung, K. J. et al. A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity. Nat. Immunol. 18, 654–664 (2017).

pubmed: 28414311 pmcid: 5436941 doi: 10.1038/ni.3728

Bae, J. et al. Activation of pattern recognition receptors in brown adipocytes induces inflammation and suppresses uncoupling protein 1 expression and mitochondrial respiration. Am. J. Physiol. Cell Physiol. 306, C918–C930 (2014).

pubmed: 24627558 doi: 10.1152/ajpcell.00249.2013

Okla, M. et al. Activation of Toll-like receptor 4 (TLR4) attenuates adaptive thermogenesis via endoplasmic reticulum stress. J. Biol. Chem. 290, 26476–26490 (2015).

pubmed: 26370079 pmcid: 4646308 doi: 10.1074/jbc.M115.677724

Bai, J. et al. Mitochondrial stress-activated cGAS-STING pathway inhibits thermogenic program and contributes to overnutrition-induced obesity in mice. Commun. Biol. 3, 257 (2020).

pubmed: 32444826 pmcid: 7244732 doi: 10.1038/s42003-020-0986-1

Eom, J. et al. Intrinsic expression of viperin regulates thermogenesis in adipose tissues. Proc. Natl Acad. Sci. USA 116, 17419–17428 (2019).

pubmed: 31341090 pmcid: 6717265 doi: 10.1073/pnas.1904480116

Mao, Y. et al. STING-IRF3 triggers endothelial inflammation in response to free fatty acid-induced mitochondrial damage in diet-induced obesity. Arterioscler. Thromb. Vasc. Biol. 37, 920–929 (2017).

pubmed: 28302626 pmcid: 5408305 doi: 10.1161/ATVBAHA.117.309017

Qiao, J. et al. A distinct role of STING in regulating glucose homeostasis through insulin sensitivity and insulin secretion. Proc. Natl Acad. Sci. USA 119, e2101848119 (2022).

pubmed: 35145023 pmcid: 8851542 doi: 10.1073/pnas.2101848119

Bai, J. et al. DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway. Proc. Natl Acad. Sci. USA 114, 12196–12201 (2017).

pubmed: 29087318 pmcid: 5699051 doi: 10.1073/pnas.1708744114

Yang, G. et al. RIG-I deficiency promotes obesity-induced insulin resistance. Pharmaceuticals 14, 1178 (2021).

pubmed: 34832960 pmcid: 8624253 doi: 10.3390/ph14111178

Chiang, S. H. et al. The protein kinase IKKɛ regulates energy balance in obese mice. Cell 138, 961–975 (2009).

pubmed: 19737522 pmcid: 2756060 doi: 10.1016/j.cell.2009.06.046

Cruz, V. H., Arner, E. N., Wynne, K. W., Scherer, P. E. & Brekken, R. A. Loss of Tbk1 kinase activity protects mice from diet-induced metabolic dysfunction. Mol. Metab. 16, 139–149 (2018).

pubmed: 29935921 pmcid: 6157474 doi: 10.1016/j.molmet.2018.06.007

Oral, E. A. et al. Inhibition of IKKɛ and TBK1 improves glucose control in a subset of patients with type 2 diabetes. Cell Metab. 26, 157–170.e7 (2017).

pubmed: 28683283 pmcid: 5663294 doi: 10.1016/j.cmet.2017.06.006

Yan, S. et al. Inflammation causes insulin resistance via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels. Preprint at BioRxiv https://doi.org/10.1101/2023.08.08.552481 (2023).

doi: 10.1101/2023.08.08.552481 pubmed: 38328043 pmcid: 10849582

Yore, M. M. et al. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell 159, 318–332 (2014).

pubmed: 25303528 pmcid: 4260972 doi: 10.1016/j.cell.2014.09.035

Erikci Ertunc, M. et al. AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice. J. Biol. Chem. 295, 5891–5905 (2020).

pubmed: 32152231 pmcid: 7196635 doi: 10.1074/jbc.RA119.012145

You, D., Chul Jung, B., Villivalam, S. D., Lim, H. W. & Kang, S. JMJD8 is a novel molecular nexus between adipocyte-intrinsic inflammation and insulin resistance. Diabetes 71, 43–59 (2021).

pubmed: 34686520 pmcid: 8763873 doi: 10.2337/db21-0596

Patel, S. J. et al. Hepatic IRF3 fuels dysglycemia in obesity through direct regulation of Ppp2r1b. Sci. Transl. Med. 14, eabh3831 (2022).

pubmed: 35320000 pmcid: 9162056 doi: 10.1126/scitranslmed.abh3831

Sangodkar, J. et al. All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase. FEBS J. 283, 1004–1024 (2016).

pubmed: 26507691 doi: 10.1111/febs.13573

Qiao, J. T. et al. Activation of the STING-IRF3 pathway promotes hepatocyte inflammation, apoptosis and induces metabolic disorders in nonalcoholic fatty liver disease. Metabolism 81, 13–24 (2018).

pubmed: 29106945 doi: 10.1016/j.metabol.2017.09.010

Liang, H., Hussey, S. E., Sanchez-Avila, A., Tantiwong, P. & Musi, N. Effect of lipopolysaccharide on inflammation and insulin action in human muscle. PLoS One 8, e63983 (2013).

pubmed: 23704966 pmcid: 3660322 doi: 10.1371/journal.pone.0063983

Otero, Y. F. et al. Enhanced glucose transport, but not phosphorylation capacity, ameliorates lipopolysaccharide-induced impairments in insulin-stimulated muscle glucose uptake. Shock 45, 677–685 (2016).

pubmed: 26682946 pmcid: 4868638 doi: 10.1097/SHK.0000000000000550

Park, S. J., Garcia Diaz, J., Um, E. & Hahn, Y. S. Major roles of Kupffer cells and macrophages in NAFLD development. Front. Endocrinol. 14, 1150118 (2023).

doi: 10.3389/fendo.2023.1150118

Blanc, M. et al. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity 38, 106–118 (2013).

pubmed: 23273843 pmcid: 3556782 doi: 10.1016/j.immuni.2012.11.004

Blanc, M. et al. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol. 9, e1000598 (2011).

pubmed: 21408089 pmcid: 3050939 doi: 10.1371/journal.pbio.1000598

Liu, S. Y. et al. Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity 38, 92–105 (2013).

pubmed: 23273844 doi: 10.1016/j.immuni.2012.11.005

Petersen, J. et al. The major cellular sterol regulatory pathway is required for Andes virus infection. PLoS Pathog. 10, e1003911 (2014).

pubmed: 24516383 pmcid: 3916400 doi: 10.1371/journal.ppat.1003911

Li, C. et al. 25-Hydroxycholesterol protects host against Zika virus infection and its associated microcephaly in a mouse model. Immunity 46, 446–456 (2017).

pubmed: 28314593 pmcid: 5957489 doi: 10.1016/j.immuni.2017.02.012

Castrillo, A. et al. Crosstalk between LXR and Toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism. Mol. Cell 12, 805–816 (2003).

pubmed: 14580333 doi: 10.1016/S1097-2765(03)00384-8

Mendoza-Herrera, K. et al. The leptin system and diet: a mini review of the current evidence. Front. Endocrinol. 12, 749050 (2021).

doi: 10.3389/fendo.2021.749050

Heyward, F. D. et al. Integrated genomic analysis of AgRP neurons reveals that IRF3 regulates leptin’s hunger-suppressing effects. Preprint at BioRxiv https://doi.org/10.1101/2022.01.03.474708 (2023).

doi: 10.1101/2022.01.03.474708

Wong, R. W. J., Ong, J. Z. L., Theardy, M. S. & Sanda, T. IRF4 as an oncogenic master transcription factor. Cancers 14, 4314 (2022).

pubmed: 36077849 pmcid: 9454692 doi: 10.3390/cancers14174314

IRF4 International Consortium et al. A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency. Sci. Immunol. 8, eade7953 (2023).

pmcid: 10825898 doi: 10.1126/sciimmunol.ade7953

Mittrucker, H. W. et al. Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function. Science 275, 540–543 (1997).

pubmed: 8999800 doi: 10.1126/science.275.5299.540

Brass, A. L., Kehrli, E., Eisenbeis, C. F., Storb, U. & Singh, H. Pip, a lymphoid-restricted IRF, contains a regulatory domain that is important for autoinhibition and ternary complex formation with the Ets factor PU.1. Genes Dev. 10, 2335–2347 (1996).

pubmed: 8824592 doi: 10.1101/gad.10.18.2335

Glasmacher, E. et al. A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science 338, 975–980 (2012).

pubmed: 22983707 pmcid: 5789805 doi: 10.1126/science.1228309

Matsuyama, T. et al. Molecular cloning of LSIRF, a lymphoid-specific member of the interferon regulatory factor family that binds the interferon-stimulated response element (ISRE). Nucleic Acids Res. 23, 2127–2136 (1995).

pubmed: 7541907 pmcid: 306999 doi: 10.1093/nar/23.12.2127

Negishi, H. et al. Negative regulation of Toll-like-receptor signaling by IRF-4. Proc. Natl Acad. Sci. USA 102, 15989–15994 (2005).

pubmed: 16236719 pmcid: 1257749 doi: 10.1073/pnas.0508327102

Cook, S. L., Franke, M. C., Sievert, E. P. & Sciammas, R. A synchronous IRF4-dependent gene regulatory network in B and helper T cells orchestrating the antibody response. Trends Immunol. 41, 614–628 (2020).

pubmed: 32467029 pmcid: 8722497 doi: 10.1016/j.it.2020.05.001

Mahnke, J. et al. Interferon regulatory factor 4 controls T

pubmed: 27762344 pmcid: 5071867 doi: 10.1038/srep35521

Man, K. et al. The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells. Nat. Immunol. 14, 1155–1165 (2013).

pubmed: 24056747 doi: 10.1038/ni.2710

Feuerer, M. et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat. Med. 15, 930–939 (2009).

pubmed: 19633656 pmcid: 3115752 doi: 10.1038/nm.2002

Spallanzani, R. G. et al. Distinct immunocyte-promoting and adipocyte-generating stromal components coordinate adipose tissue immune and metabolic tenors. Sci. Immunol. 4, eaaw3658 (2019).

pubmed: 31053654 pmcid: 6648660 doi: 10.1126/sciimmunol.aaw3658

Vasanthakumar, A. et al. The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. Nat. Immunol. 16, 276–285 (2015).

pubmed: 25599561 doi: 10.1038/ni.3085

Honma, K. et al. Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS. Proc. Natl Acad. Sci. USA 102, 16001–16006 (2005).

pubmed: 16243976 pmcid: 1276050 doi: 10.1073/pnas.0504226102

Huang, S. C. et al. Metabolic reprogramming mediated by the mTORC2-IRF4 signaling axis is essential for macrophage alternative activation. Immunity 45, 817–830 (2016).

pubmed: 27760338 pmcid: 5535820 doi: 10.1016/j.immuni.2016.09.016

Eguchi, J. et al. Interferon regulatory factor 4 regulates obesity-induced inflammation through regulation of adipose tissue macrophage polarization. Diabetes 62, 3394–3403 (2013).

pubmed: 23835343 pmcid: 3781469 doi: 10.2337/db12-1327

Satoh, T. et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat. Immunol. 11, 936–944 (2010).

pubmed: 20729857 doi: 10.1038/ni.1920

El Chartouni, C., Schwarzfischer, L. & Rehli, M. Interleukin-4 induced interferon regulatory factor (Irf) 4 participates in the regulation of alternative macrophage priming. Immunobiology 215, 821–825 (2010).

pubmed: 20580461 doi: 10.1016/j.imbio.2010.05.031

Eguchi, J. et al. Transcriptional control of adipose lipid handling by IRF4. Cell Metab. 13, 249–259 (2011).

pubmed: 21356515 pmcid: 3063358 doi: 10.1016/j.cmet.2011.02.005

DiPilato, L. M. et al. The role of PDE3B phosphorylation in the inhibition of lipolysis by insulin. Mol. Cell Biol. 35, 2752–2760 (2015).

pubmed: 26031333 pmcid: 4508315 doi: 10.1128/MCB.00422-15

Cavallari, J. F. et al. Muramyl dipeptide-based postbiotics mitigate obesity-induced insulin resistance via IRF4. Cell Metab. 25, 1063–1074.e3 (2017).

pubmed: 28434881 doi: 10.1016/j.cmet.2017.03.021

Duggan, B. M., Singh, A. M., Chan, D. Y. & Schertzer, J. D. Postbiotics engage IRF4 in adipocytes to promote sex-dependent changes in blood glucose during obesity. Physiol. Rep. 10, e15439 (2022).

pubmed: 35993451 pmcid: 9393906 doi: 10.14814/phy2.15439

Kong, X. et al. IRF4 is a key thermogenic transcriptional partner of PGC-1α. Cell 158, 69–83 (2014).

pubmed: 24995979 pmcid: 4116691 doi: 10.1016/j.cell.2014.04.049

Nguyen, K. D. et al. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 480, 104–108 (2011).

pubmed: 22101429 pmcid: 3371761 doi: 10.1038/nature10653

Qiu, Y. et al. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157, 1292–1308 (2014).

pubmed: 24906148 pmcid: 4129510 doi: 10.1016/j.cell.2014.03.066

Wu, S. et al. M2 macrophages independently promote beige adipogenesis via blocking adipocyte Ets1. Nat. Commun. 15, 1646 (2024).

pubmed: 38388532 pmcid: 10883921 doi: 10.1038/s41467-024-45899-4

Fischer, K. et al. Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis. Nat. Med. 23, 623–630 (2017).

pubmed: 28414329 pmcid: 5420449 doi: 10.1038/nm.4316

Kong, X. et al. Brown adipose tissue controls skeletal muscle function via the secretion of myostatin. Cell Metab. 28, 631–643.e3 (2018).

pubmed: 30078553 pmcid: 6170693 doi: 10.1016/j.cmet.2018.07.004

Zhu, X. et al. IRF4 in skeletal muscle regulates exercise capacity via PTG/glycogen pathway. Adv. Sci. 7, 2001502 (2020).

doi: 10.1002/advs.202001502

Yao, T. et al. Obese skeletal muscle-expressed interferon regulatory factor 4 transcriptionally regulates mitochondrial branched-chain aminotransferase reprogramming metabolome. Diabetes 71, 2256–2271 (2022).

pubmed: 35713959 pmcid: 9630087 doi: 10.2337/db22-0260

Abdualkader, A. M., Lopaschuk, G. D. & Al Batran, R. The double face of IRF4 in metabolic reprogramming. Diabetes 71, 2251–2252 (2022).

pubmed: 36265015 doi: 10.2337/dbi22-0026

Guo, S. et al. Metabolic crosstalk between skeletal muscle cells and liver through IRF4-FSTL1 in nonalcoholic steatohepatitis. Nat. Commun. 14, 6047 (2023).

pubmed: 37770480 pmcid: 10539336 doi: 10.1038/s41467-023-41832-3

Zhao, Y., Wang, X. & Nie, K. IRF1 promotes the chondrogenesis of human adipose-derived stem cells through regulating HILPDA. Tissue Cell 82, 102046 (2023).

pubmed: 36933274 doi: 10.1016/j.tice.2023.102046

Rauch, A. & Mandrup, S. Transcriptional networks controlling stromal cell differentiation. Nat. Rev. Mol. Cell Biol. 22, 465–482 (2021).

pubmed: 33837369 doi: 10.1038/s41580-021-00357-7

Friesen, M. et al. Activation of IRF1 in human adipocytes leads to phenotypes associated with metabolic disease. Stem Cell Rep. 8, 1164–1173 (2017).

doi: 10.1016/j.stemcr.2017.03.014

Shin, J. et al. SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in the lung, liver, adipose tissue, and pancreatic cells via IRF1. Metabolism 133, 155236 (2022).

pubmed: 35688210 pmcid: 9173833 doi: 10.1016/j.metabol.2022.155236

Kissig, M. et al. PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing. EMBO J. 36, 1528–1542 (2017).

pubmed: 28408438 pmcid: 5452012 doi: 10.15252/embj.201695588

Cui, H., Banerjee, S., Guo, S., Xie, N. & Liu, G. IFN regulatory factor 2 inhibits expression of glycolytic genes and lipopolysaccharide-induced proinflammatory responses in macrophages. J. Immunol. 200, 3218–3230 (2018).

pubmed: 29563175 doi: 10.4049/jimmunol.1701571

Sindhu, S. et al. Enhanced adipose expression of interferon regulatory factor (IRF)-5 associates with the signatures of metabolic inflammation in diabetic obese patients. Cells 9, 730 (2020).

pubmed: 32188105 pmcid: 7140673 doi: 10.3390/cells9030730

Dalmas, E. et al. Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nat. Med. 21, 610–618 (2015).

pubmed: 25939064 doi: 10.1038/nm.3829

Orliaguet, L. et al. Early macrophage response to obesity encompasses interferon regulatory factor 5 regulated mitochondrial architecture remodelling. Nat. Commun. 13, 5089 (2022).

pubmed: 36042203 pmcid: 9427774 doi: 10.1038/s41467-022-32813-z

Hedl, M., Yan, J. & Abraham, C. IRF5 and IRF5 disease-risk variants increase glycolysis and human M1 macrophage polarization by regulating proximal signaling and Akt2 activation. Cell Rep. 16, 2442–2455 (2016).

pubmed: 27545875 pmcid: 5165654 doi: 10.1016/j.celrep.2016.07.060

Al-Rashed, F. et al. Repetitive intermittent hyperglycemia drives the M1 polarization and inflammatory responses in THP-1 macrophages through the mechanism involving the TLR4-IRF5 pathway. Cells 9, 1892 (2020).

pubmed: 32806763 pmcid: 7463685 doi: 10.3390/cells9081892

Gallucci, S., Meka, S. & Gamero, A. M. Abnormalities of the type I interferon signaling pathway in lupus autoimmunity. Cytokine 146, 155633 (2021).

pubmed: 34340046 pmcid: 8475157 doi: 10.1016/j.cyto.2021.155633

Terrell, M. & Morel, L. The intersection of cellular and systemic metabolism: metabolic syndrome in systemic lupus erythematosus. Endocrinology 163, bqac067 (2022).

pubmed: 35560001 pmcid: 9155598 doi: 10.1210/endocr/bqac067

Wang, X. A. et al. Interferon regulatory factor 7 deficiency prevents diet-induced obesity and insulin resistance. Am. J. Physiol. Endocrinol. Metab. 305, E485–E495 (2013).

pubmed: 23695216 doi: 10.1152/ajpendo.00505.2012

Nodari, A. et al. Interferon regulatory factor 7 impairs cellular metabolism in aging adipose-derived stromal cells. J. Cell Sci. 134, jcs256230 (2021).

pubmed: 34096605 doi: 10.1242/jcs.256230

Li, Z. et al. IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma. Int. J. Biol. Sci. 18, 30–42 (2022).

pubmed: 34975316 pmcid: 8692136 doi: 10.7150/ijbs.65255

Moorman, H. R., Reategui, Y., Poschel, D. B. & Liu, K. IRF8: mechanism of action and health implications. Cells 11, 2630 (2022).

pubmed: 36078039 pmcid: 9454819 doi: 10.3390/cells11172630

Pearl, D. et al. 4E-BP-dependent translational control of Irf8 mediates adipose tissue macrophage inflammatory response. J. Immunol. 204, 2392–2400 (2020).

pubmed: 32213561 doi: 10.4049/jimmunol.1900538

Heim, M. H. The Jak-STAT pathway: cytokine signalling from the receptor to the nucleus. J. Recept. Signal. Transduct. Res. 19, 75–120 (1999).

pubmed: 10071751 doi: 10.3109/10799899909036638

Demiroz, D. et al. Listeria monocytogenes infection rewires host metabolism with regulatory input from type I interferons. PLoS Pathog. 17, e1009697 (2021).

pubmed: 34237114 pmcid: 8266069 doi: 10.1371/journal.ppat.1009697

Wang, X. A. et al. Interferon regulatory factor 9 protects against hepatic insulin resistance and steatosis in male mice. Hepatology 58, 603–616 (2013).

pubmed: 23471885 doi: 10.1002/hep.26368

Dornbos, P. et al. Evaluating human genetic support for hypothesized metabolic disease genes. Cell Metab. 34, 661–666 (2022).

pubmed: 35421386 pmcid: 9166611 doi: 10.1016/j.cmet.2022.03.011

Transcriptional control of metabolism by interferon regulatory factors.

Journal

Informations de publication

Résumé

Identifiants

Types de publication

Langues

Sous-ensembles de citation

Informations de copyright

Références

Auteurs

Zunair Ahmad (Z)

Wahab Kahloan (W)

Evan D Rosen (ED)

Classifications MeSH