Gain-of-Function Mutation of Tristetraprolin Impairs Negative Feedback Control of Macrophages In Vitro yet Has Overwhelmingly Anti-Inflammatory Consequences In Vivo

REFERENCES

• Takeuchi O, Akira S. 2010. Pattern recognition receptors and inflammation. Cell 140:805–820. https://doi.org/10.1016/j.cell.2010.01.022.
   PubMed Web of Science ®Google Scholar
• Brubaker SW, Bonham KS, Zanoni I, Kagan JC. 2015. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol 33:257–290. https://doi.org/10.1146/annurev-immunol-032414-112240.
   PubMed Web of Science ®Google Scholar
• Zak DE, Tam VC, Aderem A. 2014. Systems-level analysis of innate immunity. Annu Rev Immunol 32:547–577. https://doi.org/10.1146/annurev-immunol-032713-120254.
   PubMed Web of Science ®Google Scholar
• Hu X, Chakravarty SD, Ivashkiv LB. 2008. Regulation of interferon and Toll-like receptor signaling during macrophage activation by opposing feedforward and feedback inhibition mechanisms. Immunol Rev 226:41–56. https://doi.org/10.1111/j.1600-065X.2008.00707.x.
   PubMed Web of Science ®Google Scholar
• Abraham SM, Clark AR. 2006. Dual-specificity phosphatase 1: a critical regulator of innate immune responses. Biochem Soc Trans 34:1018–1023. https://doi.org/10.1042/BST0341018.
   PubMed Web of Science ®Google Scholar
• Bode JG, Ehlting C, Haussinger D. 2012. The macrophage response towards LPS and its control through the p38(MAPK)-STAT3 axis. Cell Signal 24:1185–1194. https://doi.org/10.1016/j.cellsig.2012.01.018.
   PubMed Web of Science ®Google Scholar
• Murray PJ, Smale ST. 2012. Restraint of inflammatory signaling by interdependent strata of negative regulatory pathways. Nat Immunol 13:916–924. https://doi.org/10.1038/ni.2391.
   PubMed Web of Science ®Google Scholar
• Kole A, Maloy KJ. 2014. Control of intestinal inflammation by interleukin-10. Curr Top Microbiol Immunol 380:19–38. https://doi.org/10.1007/978-3-662-43492-5_2.
   PubMedGoogle Scholar
• Mantovani A, Marchesi F. 2014. IL-10 and macrophages orchestrate gut homeostasis. Immunity 40:637–639. https://doi.org/10.1016/j.immuni.2014.04.015.
   PubMedGoogle Scholar
• Kobayashi M, Kweon MN, Kuwata H, Schreiber RD, Kiyono H, Takeda K, Akira S. 2003. Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice. J Clin Invest 111:1297–1308. https://doi.org/10.1172/JCI17085.
   PubMed Web of Science ®Google Scholar
• Kamada N, Hisamatsu T, Okamoto S, Sato T, Matsuoka K, Arai K, Nakai T, Hasegawa A, Inoue N, Watanabe N, Akagawa KS, Hibi T. 2005. Abnormally differentiated subsets of intestinal macrophage play a key role in Th1-dominant chronic colitis through excess production of IL-12 and IL-23 in response to bacteria. J Immunol 175:6900–6908. https://doi.org/10.4049/jimmunol.175.10.6900.
   PubMed Web of Science ®Google Scholar
• Shouval DS, Ouahed J, Biswas A, Goettel JA, Horwitz BH, Klein C, Muise AM, Snapper SB. 2014. Interleukin 10 receptor signaling: master regulator of intestinal mucosal homeostasis in mice and humans. Adv Immunol 122:177–210. https://doi.org/10.1016/B978-0-12-800267-4.00005-5.
   PubMed Web of Science ®Google Scholar
• Smith AM, Qualls JE, O'Brien K, Balouzian L, Johnson PF, Schultz-Cherry S, Smale ST, Murray PJ. 2011. A distal enhancer in Il12b is the target of transcriptional repression by the STAT3 pathway and requires the basic leucine zipper (B-ZIP) protein NFIL3. J Biol Chem 286:23582–23590. https://doi.org/10.1074/jbc.M111.249235.
   PubMedGoogle Scholar
• Shouval DS, Biswas A, Goettel JA, McCann K, Conaway E, Redhu NS, Mascanfroni ID, Al Adham Z, Lavoie S, Ibourk M, Nguyen DD, Samsom JN, Escher JC, Somech R, Weiss B, Beier R, Conklin LS, Ebens CL, Santos FG, Ferreira AR, Sherlock M, Bhan AK, Muller W, Mora JR, Quintana FJ, Klein C, Muise AM, Horwitz BH, Snapper SB. 2014. Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. Immunity 40:706–719. https://doi.org/10.1016/j.immuni.2014.03.011.
   PubMed Web of Science ®Google Scholar
• Zigmond E, Bernshtein B, Friedlander G, Walker CR, Yona S, Kim KW, Brenner O, Krauthgamer R, Varol C, Muller W, Jung S. 2014. Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis. Immunity 40:720–733. https://doi.org/10.1016/j.immuni.2014.03.012.
   PubMed Web of Science ®Google Scholar
• Engelhardt KR, Grimbacher B. 2014. IL-10 in humans: lessons from the gut, IL-10/IL-10 receptor deficiencies, and IL-10 polymorphisms. Curr Top Microbiol Immunol 380:1–18. https://doi.org/10.1007/978-3-662-43492-5_1.
   PubMedGoogle Scholar
• Hutchins AP, Diez D, Miranda-Saavedra D. 2013. The IL-10/STAT3-mediated anti-inflammatory response: recent developments and future challenges. Brief Funct Genomics 12:489–498. https://doi.org/10.1093/bfgp/elt028.
   PubMed Web of Science ®Google Scholar
• Murray PJ. 2006. Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response. Curr Opin Pharmacol 6:379–386. https://doi.org/10.1016/j.coph.2006.01.010.
   PubMed Web of Science ®Google Scholar
• Williams LM, Ricchetti G, Sarma U, Smallie T, Foxwell BM. 2004. Interleukin-10 suppression of myeloid cell activation—a continuing puzzle. Immunology 113:281–292. https://doi.org/10.1111/j.1365-2567.2004.01988.x.
   PubMed Web of Science ®Google Scholar
• Hao NB, Lu MH, Fan YH, Cao YL, Zhang ZR, Yang SM. 2012. Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol 2012:948098. https://doi.org/10.1155/2012/948098.
   PubMedGoogle Scholar
• Ouyang P, Rakus K, van Beurden SJ, Westphal AH, Davison AJ, Gatherer D, Vanderplasschen AF. 2014. IL-10 encoded by viruses: a remarkable example of independent acquisition of a cellular gene by viruses and its subsequent evolution in the viral genome. J Gen Virol 95:245–262. https://doi.org/10.1099/vir.0.058966-0.
   PubMedGoogle Scholar
• Gabrysova L, Howes A, Saraiva M, O'Garra A. 2014. The regulation of IL-10 expression. Curr Top Microbiol Immunol 380:157–190. https://doi.org/10.1007/978-3-662-43492-5_8.
   PubMed Web of Science ®Google Scholar
• MacKenzie KF, Pattison MJ, Arthur JS. 2014. Transcriptional regulation of IL-10 and its cell-specific role in vivo. Crit Rev Immunol 34:315–345. https://doi.org/10.1615/CritRevImmunol.2014010694.
   PubMed Web of Science ®Google Scholar
• Glass CK. 2015. Genetic and genomic approaches to understanding macrophage identity and function. Arterioscler Thromb Vasc Biol 35:755–762. https://doi.org/10.1161/ATVBAHA.114.304051.
   PubMedGoogle Scholar
• Medzhitov R, Horng T. 2009. Transcriptional control of the inflammatory response. Nat Rev Immunol 9:692–703. https://doi.org/10.1038/nri2634.
   PubMed Web of Science ®Google Scholar
• Schultze JL, Freeman T, Hume DA, Latz E. 2015. A transcriptional perspective on human macrophage biology. Semin Immunol 27:44–50. https://doi.org/10.1016/j.smim.2015.02.001.
   PubMedGoogle Scholar
• Smale ST, Natoli G. 2014. Transcriptional control of inflammatory responses. Cold Spring Harb Perspect Biol 6:a016261. https://doi.org/10.1101/cshperspect.a016261.
   PubMed Web of Science ®Google Scholar
• Carpenter S, Ricci EP, Mercier BC, Moore MJ, Fitzgerald KA. 2014. Post-transcriptional regulation of gene expression in innate immunity. Nat Rev Immunol 14:361–376. https://doi.org/10.1038/nri3682.
   PubMed Web of Science ®Google Scholar
• Khabar KS. 2010. Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements. Cell Mol Life Sci 67:2937–2955. https://doi.org/10.1007/s00018-010-0383-x.
   PubMedGoogle Scholar
• Brooks SA, Blackshear PJ. 2013. Tristetraprolin (TTP): interactions with mRNA and proteins, and current thoughts on mechanisms of action. Biochim Biophys Acta 1829:666–679. https://doi.org/10.1016/j.bbagrm.2013.02.003.
   PubMed Web of Science ®Google Scholar
• Patial S, Blackshear PJ. 2016. Tristetraprolin as a therapeutic target in inflammatory disease. Trends Pharmacol Sci 37:811–821. https://doi.org/10.1016/j.tips.2016.07.002.
   PubMed Web of Science ®Google Scholar
• Carballo E, Lai WS, Blackshear PJ. 1998. Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin. Science 281:1001–1005. https://doi.org/10.1126/science.281.5379.1001.
   PubMed Web of Science ®Google Scholar
• Kratochvill F, Machacek C, Vogl C, Ebner F, Sedlyarov V, Gruber AR, Hartweger H, Vielnascher R, Karaghiosoff M, Rulicke T, Muller M, Hofacker I, Lang R, Kovarik P. 2011. Tristetraprolin-driven regulatory circuit controls quality and timing of mRNA decay in inflammation. Mol Syst Biol 7:560. https://doi.org/10.1038/msb.2011.93.
   PubMed Web of Science ®Google Scholar
• Qiu LQ, Stumpo DJ, Blackshear PJ. 2012. Myeloid-specific tristetraprolin deficiency in mice results in extreme lipopolysaccharide sensitivity in an otherwise minimal phenotype. J Immunol 188:5150–5159. https://doi.org/10.4049/jimmunol.1103700.
   PubMed Web of Science ®Google Scholar
• Taylor GA, Carballo E, Lee DM, Lai WS, Thompson MJ, Patel DD, Schenkman DI, Gilkeson GS, Broxmeyer HE, Haynes BF, Blackshear PJ. 1996. A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity 4:445–454. https://doi.org/10.1016/S1074-7613(00)80411-2.
   PubMed Web of Science ®Google Scholar
• Carballo E, Blackshear PJ. 2001. Roles of tumor necrosis factor-alpha receptor subtypes in the pathogenesis of the tristetraprolin-deficiency syndrome. Blood 98:2389–2395. https://doi.org/10.1182/blood.V98.8.2389.
   PubMed Web of Science ®Google Scholar
• Tiedje C, Diaz-Munoz MD, Trulley P, Ahlfors H, Laass K, Blackshear PJ, Turner M, Gaestel M. 2016. The RNA-binding protein TTP is a global post-transcriptional regulator of feedback control in inflammation. Nucleic Acids Res 44:7418–7440. https://doi.org/10.1093/nar/gkw474.
   PubMed Web of Science ®Google Scholar
• Sedlyarov V, Fallmann J, Ebner F, Huemer J, Sneezum L, Ivin M, Kreiner K, Tanzer A, Vogl C, Hofacker I, Kovarik P. 2016. Tristetraprolin binding site atlas in the macrophage transcriptome reveals a switch for inflammation resolution. Mol Syst Biol 12:868. https://doi.org/10.15252/msb.20156628.
   PubMed Web of Science ®Google Scholar
• Gaba A, Grivennikov SI, Do MV, Stumpo DJ, Blackshear PJ, Karin M. 2012. Cutting edge: IL-10-mediated tristetraprolin induction is part of a feedback loop that controls macrophage STAT3 activation and cytokine production. J Immunol 189:2089–2093. https://doi.org/10.4049/jimmunol.1201126.
   PubMedGoogle Scholar
• Stoecklin G, Tenenbaum SA, Mayo T, Chittur SV, George AD, Baroni TE, Blackshear PJ, Anderson P. 2008. Genome-wide analysis identifies interleukin-10 mRNA as target of tristetraprolin. J Biol Chem 283:11689–11699. https://doi.org/10.1074/jbc.M709657200.
   PubMedGoogle Scholar
• Tudor C, Marchese FP, Hitti E, Aubareda A, Rawlinson L, Gaestel M, Blackshear PJ, Clark AR, Saklatvala J, Dean JL. 2009. The p38 MAPK pathway inhibits tristetraprolin-directed decay of interleukin-10 and pro-inflammatory mediator mRNAs in murine macrophages. FEBS Lett 583:1933–1938. https://doi.org/10.1016/j.febslet.2009.04.039.
   PubMedGoogle Scholar
• Dean JL, Sully G, Clark AR, Saklatvala J. 2004. The involvement of AU-rich element-binding proteins in p38 mitogen-activated protein kinase pathway-mediated mRNA stabilisation. Cell Signal 16:1113–1121. https://doi.org/10.1016/j.cellsig.2004.04.006.
   PubMed Web of Science ®Google Scholar
• Clark AR, Dean JL. 2016. The control of inflammation via the phosphorylation and dephosphorylation of tristetraprolin: a tale of two phosphatases. Biochem Soc Trans 44:1321–1337. https://doi.org/10.1042/BST20160166.
   PubMed Web of Science ®Google Scholar
• Carballo E, Cao H, Lai WS, Kennington EA, Campbell D, Blackshear PJ. 2001. Decreased sensitivity of tristetraprolin-deficient cells to p38 inhibitors suggests the involvement of tristetraprolin in the p38 signaling pathway. J Biol Chem 276:42580–42587. https://doi.org/10.1074/jbc.M104953200.
   PubMed Web of Science ®Google Scholar
• Chrestensen CA, Schroeder MJ, Shabanowitz J, Hunt DF, Pelo JW, Worthington MT, Sturgill TW. 2004. MAPKAP kinase 2 phosphorylates tristetraprolin on in vivo sites including Ser178, a site required for 14-3-3 binding. J Biol Chem 279:10176–10184. https://doi.org/10.1074/jbc.M310486200.
   PubMed Web of Science ®Google Scholar
• Stoecklin G, Stubbs T, Kedersha N, Wax S, Rigby WF, Blackwell TK, Anderson P. 2004. MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay. EMBO J 23:1313–1324. https://doi.org/10.1038/sj.emboj.7600163.
   PubMed Web of Science ®Google Scholar
• Gaestel M. 2013. What goes up must come down: molecular basis of MAPKAP kinase 2/3-dependent regulation of the inflammatory response and its inhibition. Biol Chem 394:1301–1315. https://doi.org/10.1515/hsz-2013-0197.
   PubMedGoogle Scholar
• Fabian MR, Frank F, Rouya C, Siddiqui N, Lai WS, Karetnikov A, Blackshear PJ, Nagar B, Sonenberg N. 2013. Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin. Nat Struct Mol Biol 20:735–739. https://doi.org/10.1038/nsmb.2572.
   PubMed Web of Science ®Google Scholar
• Marchese FP, Aubareda A, Tudor C, Saklatvala J, Clark AR, Dean JL. 2010. MAPKAP kinase 2 blocks tristetraprolin-directed mRNA decay by inhibiting CAF1 deadenylase recruitment. J Biol Chem 285:27590–27600. https://doi.org/10.1074/jbc.M110.136473.
   PubMed Web of Science ®Google Scholar
• Sandler H, Kreth J, Timmers HT, Stoecklin G. 2011. Not1 mediates recruitment of the deadenylase Caf1 to mRNAs targeted for degradation by tristetraprolin. Nucleic Acids Res 39:4373–4386. https://doi.org/10.1093/nar/gkr011.
   PubMed Web of Science ®Google Scholar
• Wang X, Liu Y. 2007. Regulation of innate immune response by MAP kinase phosphatase-1. Cell Signal 19:1372–1382. https://doi.org/10.1016/j.cellsig.2007.03.013.
   PubMed Web of Science ®Google Scholar
• Smallie T, Ross EA, Ammit AJ, Cunliffe HE, Tang T, Rosner DR, Ridley ML, Buckley CD, Saklatvala J, Dean JL, Clark AR. 2015. Dual-specificity phosphatase 1 and tristetraprolin cooperate to regulate macrophage responses to lipopolysaccharide. J Immunol 195:277–288. https://doi.org/10.4049/jimmunol.1402830.
   PubMed Web of Science ®Google Scholar
• Ross EA, Smallie T, Ding Q, O'Neil JD, Cunliffe HE, Tang T, Rosner DR, Klevernic I, Morrice NA, Monaco C, Cunningham AF, Buckley CD, Saklatvala J, Dean JL, Clark AR. 2015. Dominant suppression of inflammation via targeted mutation of the mRNA destabilizing protein tristetraprolin. J Immunol 195:265–276. https://doi.org/10.4049/jimmunol.1402826.
   PubMed Web of Science ®Google Scholar
• Ross EA, Naylor AJ, O'Neil JD, Crowley T, Ridley ML, Crowe J, Smallie T, Tang TJ, Turner JD, Norling LV, Dominguez S, Perlman H, Verrills NM, Kollias G, Vitek MP, Filer A, Buckley CD, Dean JL, Clark AR. 5 September 2016. Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator of pro-inflammatory gene expression. Ann Rheum Dis https://doi.org/10.1136/annrheumdis-2016-209424.
   Google Scholar
• Van Tubergen E, Vander Broek R, Lee J, Wolf G, Carey T, Bradford C, Prince M, Kirkwood KL, D'Silva NJ. 2011. Tristetraprolin regulates interleukin-6, which is correlated with tumor progression in patients with head and neck squamous cell carcinoma. Cancer 117:2677–2689. https://doi.org/10.1002/cncr.25859.
   PubMedGoogle Scholar
• Zhao W, Liu M, D'Silva NJ, Kirkwood KL. 2011. Tristetraprolin regulates interleukin-6 expression through p38 MAPK-dependent affinity changes with mRNA 3′ untranslated region. J Interferon Cytokine Res 31:629–637. https://doi.org/10.1089/jir.2010.0154.
   PubMed Web of Science ®Google Scholar
• Kratochvill F, Gratz N, Qualls JE, Van De Velde LA, Chi H, Kovarik P, Murray PJ. 2015. Tristetraprolin limits inflammatory cytokine production in tumor-associated macrophages in an mRNA decay-independent manner. Cancer Res 75:3054–3064. https://doi.org/10.1158/0008-5472.CAN-15-0205.
   PubMedGoogle Scholar
• Tao X, Gao G. 2015. Tristetraprolin recruits eukaryotic initiation factor 4E2 to repress translation of AU-rich element-containing mRNAs. Mol Cell Biol 35:3921–3932. https://doi.org/10.1128/MCB.00845-15.
   PubMed Web of Science ®Google Scholar
• Lacey DC, Achuthan A, Fleetwood AJ, Dinh H, Roiniotis J, Scholz GM, Chang MW, Beckman SK, Cook AD, Hamilton JA. 2012. Defining GM-CSF- and macrophage-CSF-dependent macrophage responses by in vitro models. J Immunol 188:5752–5765. https://doi.org/10.4049/jimmunol.1103426.
   PubMed Web of Science ®Google Scholar
• Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, Hussell T, Feldmann M, Udalova IA. 2011. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol 12:231–238. https://doi.org/10.1038/ni.1990.
   PubMed Web of Science ®Google Scholar
• Smallie T, Ricchetti G, Horwood NJ, Feldmann M, Clark AR, Williams LM. 2010. IL-10 inhibits transcription elongation of the human TNF gene in primary macrophages. J Exp Med 207:2081–2088. https://doi.org/10.1084/jem.20100414.
   PubMed Web of Science ®Google Scholar
• Adelman K, Kennedy MA, Nechaev S, Gilchrist DA, Muse GW, Chinenov Y, Rogatsky I. 2009. Immediate mediators of the inflammatory response are poised for gene activation through RNA polymerase II stalling. Proc Natl Acad Sci U S A 106:18207–18212. https://doi.org/10.1073/pnas.0910177106.
   PubMed Web of Science ®Google Scholar
• Jalonen U, Nieminen R, Vuolteenaho K, Kankaanranta H, Moilanen E. 2006. Down-regulation of tristetraprolin expression results in enhanced IL-12 and MIP-2 production and reduced MIP-3alpha synthesis in activated macrophages. Mediators Inflamm 2006:40691. https://doi.org/10.1155/MI/2006/40691.
   PubMedGoogle Scholar
• Molle C, Zhang T, Ysebrant de Lendonck L, Gueydan C, Andrianne M, Sherer F, Van Simaeys G, Blackshear PJ, Leo O, Goriely S. 2013. Tristetraprolin regulation of interleukin 23 mRNA stability prevents a spontaneous inflammatory disease. J Exp Med 210:1675–1684. https://doi.org/10.1084/jem.20120707.
   PubMed Web of Science ®Google Scholar
• Gu L, Ning H, Qian X, Huang Q, Hou R, Almourani R, Fu M, Blackshear PJ, Liu J. 2013. Suppression of IL-12 production by tristetraprolin through blocking NF-kcyB nuclear translocation. J Immunol 191:3922–3930. https://doi.org/10.4049/jimmunol.1300126.
   PubMedGoogle Scholar