Volume 12 Issue 3
Mar.  2021
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Boyi Cong, Qian Zhang, Xuetao Cao. The function and regulation of TET2 in innate immunity and inflammation[J]. Protein&Cell, 2021, 12(3): 165-173. doi: 10.1007/s13238-020-00796-6
Citation: Boyi Cong, Qian Zhang, Xuetao Cao. The function and regulation of TET2 in innate immunity and inflammation[J]. Protein&Cell, 2021, 12(3): 165-173. doi: 10.1007/s13238-020-00796-6

The function and regulation of TET2 in innate immunity and inflammation

doi: 10.1007/s13238-020-00796-6
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We thank Dr. Bingjing Wang for helpful discussion. This work was supported by grants from the National Natural Science Foundation of China (81788101, 81922032) and CAMS Innovation Fund for Medical Sciences (2016-12M-1-003).

  • Received Date: 2020-07-07
  • Rev Recd Date: 2020-09-15
  • Publish Date: 2021-03-12
  • TET2, a member of ten-eleven translocation (TET) family as α-ketoglutarate- and Fe2+-dependent dioxygenase catalyzing the iterative oxidation of 5-methylcytosine (5mC), has been widely recognized to be an important regulator for normal hematopoiesis especially myelopoiesis. Mutation and dysregulation of TET2 contribute to the development of multiple hematological malignancies. Recent studies reveal that TET2 also plays an important role in innate immune homeostasis by promoting DNA demethylation or independent of its enzymatic activity. Here, we focus on the functions of TET2 in the initiation and resolution of inflammation through epigenetic regulation and signaling network. In addition, we highlight regulation of TET2 at various molecular levels as well as the correlated inflammatory diseases, which will provide the insight to intervene in the pathological process caused by TET2 dysregulation.
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  • [1]
    Alvarez-Errico D, Vento-Tormo R, Sieweke M, Ballestar E (2015) Epigenetic control of myeloid cell differentiation, identity and function. Nat Rev Immunol 15:7-17
    [2]
    Bauer C, Gobel K, Nagaraj N, Colantuoni C, Wang M, Muller U, Kremmer E, Rottach A, Leonhardt H (2015) Phosphorylation of TET proteins is regulated via O-GlcNAcylation by the O-linked N-acetylglucosamine transferase (OGT). J Biol Chem 290:4801-4812
    [3]
    Blaschke K, Ebata KT, Karimi MM, Zepeda-Martinez JA, Goyal P, Mahapatra S, Tam A, Laird DJ, Hirst M, Rao A et al (2013) Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature 500:222-226
    [4]
    Buckley CD, Gilroy DW, Serhan CN, Stockinger B, Tak PP (2013) The resolution of inflammation. Nat Rev Immunol 13:59-66
    [5]
    Cao X (2016) Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease. Nat Rev Immunol 16:35-50
    [6]
    Chen LL, Lin HP, Zhou WJ, He CX, Zhang ZY, Cheng ZL, Song JB, Liu P, Chen XY, Xia YK et al (2018) SNIP1 recruits TET2 to regulate c-MYC target genes and cellular DNA damage response. Cell Rep 25(1485-1500):e1484
    [7]
    Cull AH, Mahendru D, Snetsinger B, Good D, Tyryshkin K, Chesney A, Ghorab Z, Reis M, Buckstein R, Wells RA et al (2018) Overexpression of Arginase 1 is linked to DNMT3A and TET2 mutations in lower-grade myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Res 65:5-13
    [8]
    Cull AH, Snetsinger B, Buckstein R, Wells RA, Rauh MJ (2017) TET2 restrains inflammatory gene expression in macrophages. Exp Hematol 55(56-70):e13
    [9]
    de Andres MC, Perez-Pampin E, Calaza M, Santaclara FJ, Ortea I, Gomez-Reino JJ, Gonzalez A (2015) Assessment of global DNA methylation in peripheral blood cell subpopulations of early rheumatoid arthritis before and after methotrexate. Arthritis Res Ther 17:233
    [10]
    Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A, Kosmider O, Le Couedic JP, Robert F, Alberdi A et al (2009) Mutation in TET2 in myeloid cancers. N Engl J Med 360:2289-2301
    [11]
    Fu L, Guerrero CR, Zhong N, Amato NJ, Liu Y, Liu S, Cai Q, Ji D, Jin SG, Niedernhofer LJ et al (2014) Tet-mediated formation of 5-hydroxymethylcytosine in RNA. J Am Chem Soc 136:11582-11585
    [12]
    Fuster JJ, MacLauchlan S, Zuriaga MA, Polackal MN, Ostriker AC, Chakraborty R, Wu CL, Sano S, Muralidharan S, Rius C et al (2017) Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 355:842-847
    [13]
    Gong D, Zhang Q, Chen LY, Yu XH, Wang G, Zou J, Zheng XL, Zhang DW, Yin WD, Tang CK (2019) Coiled-coil domaincontaining 80 accelerates atherosclerosis development through decreasing lipoprotein lipase expression via ERK1/2 phosphorylation and TET2 expression. Eur J Pharmacol 843:177-189
    [14]
    Guallar D, Bi X, Pardavila JA, Huang X, Saenz C, Shi X, Zhou H, Faiola F, Ding J, Haruehanroengra P et al (2018) RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. Nat Genet 50:443-451
    [15]
    He C, Sidoli S, Warneford-Thomson R, Tatomer DC, Wilusz JE, Garcia BA, Bonasio R (2016) High-resolution mapping of RNAbinding regions in the nuclear proteome of embryonic stem cells. Mol Cell 64:416-430
    [16]
    He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L et al (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333:1303-1307
    [17]
    Hore TA, von Meyenn F, Ravichandran M, Bachman M, Ficz G, Oxley D, Santos F, Balasubramanian S, Jurkowski TP, Reik W (2016) Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naive pluripotency by complementary mechanisms. Proc Natl Acad Sci USA 113:12202-12207
    [18]
    Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333:1300-1303
    [19]
    Jeong JJ, Gu X, Nie J, Sundaravel S, Liu H, Kuo WL, Bhagat TD, Pradhan K, Cao J, Nischal S et al (2019) Cytokine-regulated phosphorylation and activation of TET2 by JAK2 in hematopoiesis. Cancer Discov 9:778-795
    [20]
    Jiang S, Yan W, Wang SE, Baltimore D (2019) Dual mechanisms of posttranscriptional regulation of TET2 by Let-7 microRNA in macrophages. Proc Natl Acad Sci USA 116(25):12416-12421
    [21]
    Jiao J, Jin Y, Zheng M, Zhang H, Yuan M, Lv Z, Odhiambo W, Yu X, Zhang P, Li C et al (2019) AID and TET2 co-operation modulates FANCA expression by active demethylation in diffuse large B cell lymphoma. Clin Exp Immunol 195:190-201
    [22]
    Jones PA (2012) Functions of DNA methylation:islands, start sites, gene bodies and beyond. Nat Rev Genet 13:484-492
    [23]
    Kallin EM, Rodriguez-Ubreva J, Christensen J, Cimmino L, Aifantis I, Helin K, Ballestar E, Graf T (2012) TET2 facilitates the derepression of myeloid target genes during CEBPalpha-induced transdifferentiation of pre-B cells. Mol Cell 48:266-276
    [24]
    Killian JK, Kim SY, Miettinen M, Smith C, Merino M, Tsokos M, Quezado M, Smith WI Jr, Jahromi MS, Xekouki P et al (2013) Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor. Cancer Discov 3:648-657
    [25]
    Klutstein M, Nejman D, Greenfield R, Cedar H (2016) DNA methylation in cancer and aging. Cancer Res 76:3446-3450
    [26]
    Ko M, An J, Bandukwala HS, Chavez L, Aijo T, Pastor WA, Segal MF, Li H, Koh KP, Lahdesmaki H et al (2013) Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX. Nature 497:122-126
    [27]
    Kundu A, Shelar S, Ghosh A, Ballestas M, Kirkman R, Nam HY, Brinkley G, Karki S, Mobley JA, Bae S et al (2020)14-3-3 proteins protect AMPK-phosphorylated ten-eleven translocation-2(TET2) from PP2A-mediated dephosphorylation. J Biol Chem. 295(6):1754-1766
    [28]
    Langemeijer SM, Kuiper RP, Berends M, Knops R, Aslanyan MG, Massop M, Stevens-Linders E, van Hoogen P, van Kessel AG, Raymakers RA et al (2009) Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet 41:838-842
    [29]
    Li B, Zang G, Zhong W, Chen R, Zhang Y, Yang P, Yan J (2020) Activation of CD137 signaling promotes neointimal formation by attenuating TET2 and transferrring from endothelial cell-derived exosomes to vascular smooth muscle cells. Biomed Pharmacother 121:109593
    [30]
    Lio CJ, Rao A (2019) TET enzymes and 5hmC in adaptive and innate immune systems. Front Immunol 10:210
    [31]
    Liu R, Jin Y, Tang WH, Qin L, Zhang X, Tellides G, Hwa J, Yu J, Martin KA (2013) Ten-eleven translocation-2(TET2) is a master regulator of smooth muscle cell plasticity. Circulation 128:2047-2057
    [32]
    Loenarz C, Schofield CJ (2011) Physiological and biochemical aspects of hydroxylations and demethylations catalyzed by human 2-oxoglutarate oxygenases. Trends Biochem Sci 36:7-18
    [33]
    Lv L, Wang Q, Xu Y, Tsao LC, Nakagawa T, Guo H, Su L, Xiong Y (2018) Vpr targets TET2 for degradation by CRL4(VprBP) E3 ligase to sustain IL-6 expression and enhance HIV-1 replication. Mol Cell 70(961-970):e965
    [34]
    Ma S, Wan X, Deng Z, Shi L, Hao C, Zhou Z, Zhou C, Fang Y, Liu J, Yang J et al (2017) Epigenetic regulator CXXC5 recruits DNA demethylase TET2 to regulate TLR7/9-elicited IFN response in pDCs. J Exp Med 214:1471-1491
    [35]
    MacFarlane AJ, Strom A, Scott FW (2009) Epigenetics:deciphering how environmental factors may modify autoimmune type 1 diabetes. Mamm Genome 20:624-632
    [36]
    Meda F, Folci M, Baccarelli A, Selmi C (2011) The epigenetics of autoimmunity. Cell Mol Immunol 8:226-236
    [37]
    Medzhitov R (2008) Origin and physiological roles of inflammation. Nature 454:428-435
    [38]
    Minor EA, Court BL, Young JI, Wang G (2013) Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine. J Biol Chem 288:13669-13674
    [39]
    Montagner S, Leoni C, Emming S, Della Chiara G, Balestrieri C, Barozzi I, Piccolo V, Togher S, Ko M, Rao A et al (2016) TET2 regulates mast cell differentiation and proliferation through catalytic and non-catalytic activities. Cell Rep 15:1566-1579
    [40]
    Nakagawa T, Lv L, Nakagawa M, Yu Y, Yu C, D'Alessio AC, Nakayama K, Fan HY, Chen X, Xiong Y (2015) CRL4(VprBP) E3 ligase promotes monoubiquitylation and chromatin binding of TET dioxygenases. Mol Cell 57:247-260
    [41]
    O'Neill LA, Golenbock D, Bowie AG (2013) The history of Toll-like receptors-redefining innate immunity. Nat Rev Immunol 13:453-460
    [42]
    Pan W, Zhu S, Qu K, Meeth K, Cheng J, He K, Ma H, Liao Y, Wen X, Roden C et al (2017) The DNA methylcytosine dioxygenase TET2 sustains immunosuppressive function of tumor-infiltrating myeloid cells to promote melanoma progression. Immunity 47 (284-297):e285
    [43]
    Pastor WA, Aravind L, Rao A (2013) TETonic shift:biological roles of TET proteins in DNA demethylation and transcription. Nat Rev Mol Cell Biol 14:341-356
    [44]
    Quivoron C, Couronne L, Della Valle V, Lopez CK, Plo I, WagnerBallon O, Do Cruzeiro M, Delhommeau F, Arnulf B, Stern MH et al (2011) TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell 20:25-38
    [45]
    Ren S, Xu Y (2019) AC016405.3, a novel long noncoding RNA, acts as a tumor suppressor through modulation of TET2 by microRNA-19a-5p sponging in glioblastoma. Cancer Sci 110:1621-1632
    [46]
    Scherm MG, Serr I, Zahm AM, Schug J, Bellusci S, Manfredini R, Salb VK, Gerlach K, Weigmann B, Ziegler AG et al (2019) miRNA142-3p targets TET2 and impairs Treg differentiation and stability in models of type 1 diabetes. Nat Commun 10:5697
    [47]
    Shen Q, Zhang Q, Shi Y, Shi Q, Jiang Y, Gu Y, Li Z, Li X, Zhao K, Wang C et al (2018) TET2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation. Nature 554:123-127
    [48]
    Smith ZD, Meissner A (2013) DNA methylation:roles in mammalian development. Nat Rev Genet 14:204-220
    [49]
    Stefan-Lifshitz M, Karakose E, Cui L, Ettela A, Yi Z, Zhang W, Tomer Y (2019) Epigenetic modulation of beta cells by interferon-alpha via PNPT1/mir-26a/TET2 triggers autoimmune diabetes. JCI Insight 4(5):e126663
    [50]
    Sun F, Abreu-Rodriguez I, Ye S, Gay S, Distler O, Neidhart M, Karouzakis E (2019) TET1 is an important transcriptional activator of TNFalpha expression in macrophages. PLoS One 14:e0218551
    [51]
    Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L et al (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930-935
    [52]
    Tanaka S, Ise W, Inoue T, Ito A, Ono C, Shima Y, Sakakibara S, Nakayama M, Fujii K, Miura I et al (2020) TET2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity. Nat Immunol. 31:950-961
    [53]
    Wang Y, Xiao M, Chen X, Chen L, Xu Y, Lv L, Wang P, Yang H, Ma S, Lin H et al (2015) WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation. Mol Cell 57:662-673
    [54]
    Wang Y, Zhang Y (2014) Regulation of TET protein stability by calpains. Cell Rep 6:278-284
    [55]
    Wu D, Hu D, Chen H, Shi G, Fetahu IS, Wu F, Rabidou K, Fang R, Tan L, Xu S et al (2018) Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer. Nature 559:637-641
    [56]
    Wu X, Zhang Y (2017) TET-mediated active DNA demethylation:mechanism, function and beyond. Nat Rev Genet 18:517-534
    [57]
    Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT et al (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 19:17-30
    [58]
    Xue S, Liu C, Sun X, Li W, Zhang C, Zhou X, Lu Y, Xiao J, Li C, Xu X et al (2016) TET3 Inhibits Type I IFN Production Independent of DNA Demethylation. Cell Rep 16:1096-1105
    [59]
    Yang H, Lin H, Xu H, Zhang L, Cheng L, Wen B, Shou J, Guan K, Xiong Y, Ye D (2014) TET-catalyzed 5-methylcytosine hydroxylation is dynamically regulated by metabolites. Cell Res 24:1017-1020
    [60]
    Yang L, Zhang Q, Wu Q, Wei Y, Yu J, Mu J, Zhang J, Zeng W, Feng B (2018) Effect of TET2 on the pathogenesis of diabetic nephropathy through activation of transforming growth factor beta1 expression via DNA demethylation. Life Sci 207:127-137
    [61]
    Yang R, Qu C, Zhou Y, Konkel JE, Shi S, Liu Y, Chen C, Liu S, Liu D, Chen Y et al (2015) Hydrogen sulfide promotes Tet1-and TET2-mediated Foxp3 demethylation to drive regulatory T cell differentiation and maintain immune homeostasis. Immunity 43:251-263
    [62]
    Yin R, Mo J, Dai J, Wang H (2017) Nickel (II) Inhibits Tet-mediated 5-methylcytosine oxidation by high affinity displacement of the cofactor iron (II). ACS Chem Biol 12:1494-1498
    [63]
    Yue X, Lio CJ, Samaniego-Castruita D, Li X, Rao A (2019) Loss of TET2 and TET3 in regulatory T cells unleashes effector function. Nat Commun 10:2011
    [64]
    Yue X, Trifari S, Aijo T, Tsagaratou A, Pastor WA, Zepeda-Martinez JA, Lio CW, Li X, Huang Y, Vijayanand P et al (2016) Control of Foxp3 stability through modulation of TET activity. J Exp Med 213:377-397
    [65]
    Zhang Q, Zhao K, Shen Q, Han Y, Gu Y, Li X, Zhao D, Liu Y, Wang C, Zhang X et al (2015) TET2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature 525:389-393
    [66]
    Zhang P, Chu T, Dedousis N, Mantell BS, Sipula I, Li L, Bunce KD, Shaw PA, Katz LS, Zhu J et al (2017a) DNA methylation alters transcriptional rates of differentially expressed genes and contributes to pathophysiology in mice fed a high fat diet. Mol Metab 6:327-339
    [67]
    Zhang YW, Wang Z, Xie W, Cai Y, Xia L, Easwaran H, Luo J, Yen RC, Li Y, Baylin SB (2017b) Acetylation enhances TET2 function in protecting against abnormal DNA methylation during oxidative stress. Mol Cell 65:323-335
    [68]
    Zhang TJ, Zhou JD, Yang DQ, Wang YX, Wen XM, Guo H, Yang L, Lian XY, Lin J, Qian J (2018) TET2 expression is a potential prognostic and predictive biomarker in cytogenetically normal acute myeloid leukemia. J Cell Physiol 233:5838-5846
    [69]
    Zhang Q, Cao X (2019) Epigenetic regulation of the innate immune response to infection. Nat Rev Immunol. 19:417-432
    [70]
    Zhang J, Tan P, Guo L, Gong J, Ma J, Li J, Lee M, Fang S, Jing J, Johnson G et al (2019a) p53-dependent autophagic degradation of TET2 modulates cancer therapeutic resistance. Oncogene 38:1905-1919
    [71]
    Zhang T, Guan X, Choi UL, Dong Q, Lam MMT, Zeng J, Xiong J, Wang X, Poon TCW, Zhang H et al (2019b) Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation. Epigenetics Chromatin 12:32
    [72]
    Zhaolin Z, Jiaojiao C, Peng W, Yami L, Tingting Z, Jun T, Shiyuan W, Jinyan X, Dangheng W, Zhisheng J et al (2019) OxLDL induces vascular endothelial cell pyroptosis through miR-125a-5p/TET2 pathway. J Cell Physiol 234:7475-7491
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