1932

Abstract

The innate immune response is a rapid response to pathogens or danger signals. It is precisely activated not only to efficiently eliminate pathogens but also to avoid excessive inflammation and tissue damage. -Regulatory element–associated chromatin architecture shaped by epigenetic factors, which we define as the epiregulome, endows innate immune cells with specialized phenotypes and unique functions by establishing cell-specific gene expression patterns, and it also contributes to resolution of the inflammatory response. In this review, we focus on two aspects: () how niche signals during lineage commitment or following infection and pathogenic stress program epiregulomes by regulating gene expression levels, enzymatic activities, or gene-specific targeting of chromatin modifiers and () how the programed epiregulomes in turn mediate regulation of gene-specific expression, which contributes to controlling the development of innate cells, or the response to infection and inflammation, in a timely manner. We also discuss the effects of innate immunometabolic rewiring on epiregulomes and speculate on several future challenges to be encountered during the exploration of the master regulators of epiregulomes in innate immunity and inflammation.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-093019-123619
2021-04-26
2024-06-13
Loading full text...

Full text loading...

/deliver/fulltext/immunol/39/1/annurev-immunol-093019-123619.html?itemId=/content/journals/10.1146/annurev-immunol-093019-123619&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Hoffmann JA. 2003. The immune response of Drosophila. Nature 426:33–38
    [Google Scholar]
  2. 2. 
    Beutler B, Rietschel ET. 2003. Innate immune sensing and its roots: the story of endotoxin. Nat. Rev. Immunol. 3:169–76
    [Google Scholar]
  3. 3. 
    Medzhitov R. 2001. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1:135–45
    [Google Scholar]
  4. 4. 
    Cao X. 2016. Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease. Nat. Rev. Immunol. 16:35–50
    [Google Scholar]
  5. 5. 
    Netea MG, Joosten LA, Latz E, Mills KH, Natoli G et al. 2016. Trained immunity: a program of innate immune memory in health and disease. Science 352:aaf1098
    [Google Scholar]
  6. 6. 
    Zhang Q, Cao X. 2019. Epigenetic regulation of the innate immune response to infection. Nat. Rev. Immunol. 19:417–32
    [Google Scholar]
  7. 7. 
    Martins R, Carlos AR, Braza F, Thompson JA, Bastos-Amador P et al. 2019. Disease tolerance as an inherent component of immunity. Annu. Rev. Immunol. 37:405–37
    [Google Scholar]
  8. 8. 
    Amatullah H, Jeffrey KL. 2020. Epigenome-metabolome-microbiome axis in health and IBD. Curr. Opin. Microbiol. 56:97–108
    [Google Scholar]
  9. 9. 
    Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. 2020. The trinity of COVID-19: immunity, inflammation and intervention. . Nat. Rev. Immunol. 20:6363–74
    [Google Scholar]
  10. 10. 
    Cao X. 2020. COVID-19: immunopathology and its implications for therapy. . Nat. Rev. Immunol. 20:5269–270
    [Google Scholar]
  11. 11. 
    Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M et al. 2020. Defining trained immunity and its role in health and disease. Nat. Rev. Immunol. 20:6375–88
    [Google Scholar]
  12. 12. 
    Mantovani A, Ponzetta A, Inforzato A, Jaillon S. 2019. Innate immunity, inflammation and tumour progression: double-edged swords. J. Intern. Med. 285:524–32
    [Google Scholar]
  13. 13. 
    Ryan DG, O'Neill LAJ 2020. Krebs cycle reborn in macrophage immunometabolism. Annu. Rev. Immunol. 38:289–313
    [Google Scholar]
  14. 14. 
    Allis CD, Jenuwein T. 2016. The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 17:487–500
    [Google Scholar]
  15. 15. 
    Chaudhri VK, Dienger-Stambaugh K, Wu Z, Shrestha M, Singh H. 2020. Charting the cis-regulome of activated B cells by coupling structural and functional genomics. Nat. Immunol. 21:210–20
    [Google Scholar]
  16. 16. 
    ENCODE Proj. Consort. 2004. The ENCODE (ENCyclopedia Of DNA Elements) project. Science 306:636–40
    [Google Scholar]
  17. 17. 
    Shih HY, Sciume G, Mikami Y, Guo L, Sun HW et al. 2016. Developmental acquisition of regulomes underlies innate lymphoid cell functionality. Cell 165:1120–33
    [Google Scholar]
  18. 18. 
    Bird A. 2007. Perceptions of epigenetics. Nature 447:396–98
    [Google Scholar]
  19. 19. 
    Cheng X, Kumar S, Posfai J, Pflugrath JW, Roberts RJ. 1993. Crystal structure of the HhaI DNA methyltransferase complexed with S-adenosyl-l-methionine. Cell 74:299–307
    [Google Scholar]
  20. 20. 
    Ramsahoye BH, Biniszkiewicz D, Lyko F, Clark V, Bird AP, Jaenisch R 2000. Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. PNAS 97:5237–42
    [Google Scholar]
  21. 21. 
    Xie W, Barr CL, Kim A, Yue F, Lee AY et al. 2012. Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome. Cell 148:816–31
    [Google Scholar]
  22. 22. 
    Jones PA. 2012. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13:484–92
    [Google Scholar]
  23. 23. 
    Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H et al. 2009. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–35
    [Google Scholar]
  24. 24. 
    Wu X, Zhang Y. 2017. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat. Rev. Genet. 18:517–34
    [Google Scholar]
  25. 25. 
    Lio CJ, Rao A. 2019. TET enzymes and 5hmC in adaptive and innate immune systems. Front. Immunol. 10:210
    [Google Scholar]
  26. 26. 
    Xie Q, Wu TP, Gimple RC, Li Z, Prager BC et al. 2018. N6-Methyladenine DNA modification in glioblastoma. Cell 175:1228–43.e20
    [Google Scholar]
  27. 27. 
    Li Z, Zhao S, Nelakanti RV, Lin K, Wu TP et al. 2020. N6-Methyladenine in DNA antagonizes SATB1 in early development. Nature 583:7817625–30
    [Google Scholar]
  28. 28. 
    Musheev MU, Baumgärtner A, Krebs L, Niehrs C. 2020. The origin of genomic N6-Methyl-deoxyadenosine in mammalian cells. Nat. Chem. Biol. 16:6630–34
    [Google Scholar]
  29. 29. 
    Strahl BD, Allis CD. 2000. The language of covalent histone modifications. Nature 403:41–45
    [Google Scholar]
  30. 30. 
    Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG et al. 1996. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84:843–51
    [Google Scholar]
  31. 31. 
    Smale ST. 2012. Transcriptional regulation in the innate immune system. Curr. Opin. Immunol. 24:51–57
    [Google Scholar]
  32. 32. 
    Fukaya T, Lim B, Levine M. 2016. Enhancer control of transcriptional bursting. Cell 166:358–68
    [Google Scholar]
  33. 33. 
    Zhao S, Yue Y, Li Y, Li H. 2019. Identification and characterization of ‘readers’ for novel histone modifications. Curr. Opin. Chem. Biol. 51:57–65
    [Google Scholar]
  34. 34. 
    Sabari BR, Zhang D, Allis CD, Zhao Y. 2017. Metabolic regulation of gene expression through histone acylations. Nat. Rev. Mol. Cell Biol. 18:90–101
    [Google Scholar]
  35. 35. 
    Flaus A, Martin DM, Barton GJ, Owen-Hughes T. 2006. Identification of multiple distinct Snf2 subfamilies with conserved structural motifs. Nucleic Acids Res 34:2887–905
    [Google Scholar]
  36. 36. 
    Ramirez-Carrozzi VR, Nazarian AA, Li CC, Gore SL, Sridharan R et al. 2006. Selective and antagonistic functions of SWI/SNF and Mi-2β nucleosome remodeling complexes during an inflammatory response. Genes Dev 20:282–96
    [Google Scholar]
  37. 37. 
    Cramer P. 2019. Organization and regulation of gene transcription. Nature 573:45–54
    [Google Scholar]
  38. 38. 
    Zheng H, Xie W. 2019. The role of 3D genome organization in development and cell differentiation. Nat. Rev. Mol. Cell Biol. 20:535–50
    [Google Scholar]
  39. 39. 
    Atianand MK, Caffrey DR, Fitzgerald KA. 2017. Immunobiology of long noncoding RNAs. Annu. Rev. Immunol. 35:177–98
    [Google Scholar]
  40. 40. 
    Nachtergaele S, He C. 2018. Chemical modifications in the life of an mRNA transcript. Annu. Rev. Genet. 52:349–72
    [Google Scholar]
  41. 41. 
    Linder B, Jaffrey SR. 2019. Discovering and mapping the modified nucleotides that comprise the epitranscriptome of mRNA. Cold Spring Harb. Perspect. Biol. 11:6a032201
    [Google Scholar]
  42. 42. 
    Mitroulis I, Ruppova K, Wang B, Chen LS, Grzybek M et al. 2018. Modulation of myelopoiesis progenitors is an integral component of trained immunity. Cell 172:147–61.e12
    [Google Scholar]
  43. 43. 
    Schultze JL, Mass E, Schlitzer A. 2019. Emerging principles in myelopoiesis at homeostasis and during infection and inflammation. Immunity 50:288–301
    [Google Scholar]
  44. 44. 
    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
    [Google Scholar]
  45. 45. 
    Bagadia P, Huang X, Liu TT, Murphy KM. 2019. Shared transcriptional control of innate lymphoid cell and dendritic cell development. Annu. Rev. Cell Dev. Biol. 35:381–406
    [Google Scholar]
  46. 46. 
    Ginhoux F, Guilliams M. 2016. Tissue-resident macrophage ontogeny and homeostasis. Immunity 44:439–49
    [Google Scholar]
  47. 47. 
    T'Jonck W, Guilliams M, Bonnardel J 2018. Niche signals and transcription factors involved in tissue-resident macrophage development. Cell Immunol 330:43–53
    [Google Scholar]
  48. 48. 
    Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H et al. 2014. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159:1312–26
    [Google Scholar]
  49. 49. 
    Sakai M, Troutman TD, Seidman JS, Ouyang Z, Spann NJ et al. 2019. Liver-derived signals sequentially reprogram myeloid enhancers to initiate and maintain Kupffer cell identity. Immunity 51:655–70.e8
    [Google Scholar]
  50. 50. 
    Seidman JS, Troutman TD, Sakai M, Gola A, Spann NJ et al. 2020. Niche-specific reprogramming of epigenetic landscapes drives myeloid cell diversity in nonalcoholic steatohepatitis. Immunity 52:61057–74.e7
    [Google Scholar]
  51. 51. 
    Murray PJ. 2017. Macrophage polarization. Annu. Rev. Physiol. 79:541–66
    [Google Scholar]
  52. 52. 
    Ishii M, Wen H, Corsa CA, Liu T, Coelho AL et al. 2009. Epigenetic regulation of the alternatively activated macrophage phenotype. Blood 114:3244–54
    [Google Scholar]
  53. 53. 
    Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y et al. 2010. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat. Immunol. 11:936–44
    [Google Scholar]
  54. 54. 
    Huang M, Wang Q, Long F, Di Y, Wang J et al. 2020. Jmjd3 regulates inflammasome activation and aggravates DSS-induced colitis in mice. FASEB J 34:4107–19
    [Google Scholar]
  55. 55. 
    Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V et al. 2007. Macrophage-specific PPARγ controls alternative activation and improves insulin resistance. Nature 447:1116–20
    [Google Scholar]
  56. 56. 
    Daniel B, Nagy G, Czimmerer Z, Horvath A, Hammers DW et al. 2018. The nuclear receptor PPARγ controls progressive macrophage polarization as a ligand-insensitive epigenomic ratchet of transcriptional memory. Immunity 49:615–26.e6
    [Google Scholar]
  57. 57. 
    Tikhanovich I, Zhao J, Olson J, Adams A, Taylor R et al. 2017. Protein arginine methyltransferase 1 modulates innate immune responses through regulation of peroxisome proliferator-activated receptor γ-dependent macrophage differentiation. J. Biol. Chem. 292:6882–94
    [Google Scholar]
  58. 58. 
    Yang X, Wang X, Liu D, Yu L, Xue B, Shi H. 2014. Epigenetic regulation of macrophage polarization by DNA methyltransferase 3b. Mol. Endocrinol. 28:565–74
    [Google Scholar]
  59. 59. 
    Mullican SE, Gaddis CA, Alenghat T, Nair MG, Giacomin PR et al. 2011. Histone deacetylase 3 is an epigenomic brake in macrophage alternative activation. Genes Dev 25:2480–88
    [Google Scholar]
  60. 60. 
    Ghisletti S, Barozzi I, Mietton F, Polletti S, De Santa F et al. 2010. Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity 32:317–28
    [Google Scholar]
  61. 61. 
    Kaikkonen MU, Spann NJ, Heinz S, Romanoski CE, Allison KA et al. 2013. Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription. Mol. Cell 51:310–25
    [Google Scholar]
  62. 62. 
    Czimmerer Z, Daniel B, Horvath A, Rückerl D, Nagy G et al. 2018. The transcription factor STAT6 mediates direct repression of inflammatory enhancers and limits activation of alternatively polarized macrophages. Immunity 48:75–90.e6
    [Google Scholar]
  63. 63. 
    Nguyen HCB, Adlanmerini M, Hauck AK, Lazar MA. 2020. Dichotomous engagement of HDAC3 activity governs inflammatory responses. Nature 584:7820286–90
    [Google Scholar]
  64. 64. 
    Han X, Huang S, Xue P, Fu J, Liu L et al. 2019. LncRNA PTPRE-AS1 modulates M2 macrophage activation and inflammatory diseases by epigenetic promotion of PTPRE. Sci. Adv. 5:eaax9230
    [Google Scholar]
  65. 65. 
    Kuznetsova T, Prange KHM, Glass CK, de Winther MPJ. 2020. Transcriptional and epigenetic regulation of macrophages in atherosclerosis. Nat. Rev. Cardiol. 17:216–28
    [Google Scholar]
  66. 66. 
    Yeh H, Ikezu T. 2019. Transcriptional and epigenetic regulation of microglia in health and disease. Trends Mol. Med. 25:96–111
    [Google Scholar]
  67. 67. 
    Kimball AS, Davis FM, denDekker A, Joshi AD, Schaller MA et al. 2019. The histone methyltransferase Setdb2 modulates macrophage phenotype and uric acid production in diabetic wound repair. Immunity 51:258–71.e5
    [Google Scholar]
  68. 68. 
    denDekker AD, Davis FM, Joshi AD, Wolf SJ, Allen R et al. 2020. TNF-α regulates diabetic macrophage function through the histone acetyltransferase MOF. JCI Insight 5:5e132306
    [Google Scholar]
  69. 69. 
    Davis FM, denDekker A, Kimball A, Joshi AD, El Azzouny M et al. 2020. Epigenetic regulation of TLR4 in diabetic macrophages modulates immunometabolism and wound repair. J. Immunol. 204:2503–13
    [Google Scholar]
  70. 70. 
    Yan J, Tie G, Wang S, Tutto A, DeMarco N et al. 2018. Diabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages. Nat. Commun. 9:33
    [Google Scholar]
  71. 71. 
    Martinez FO, Gordon S. 2014. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 6:13
    [Google Scholar]
  72. 72. 
    Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW et al. 2014. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41:14–20
    [Google Scholar]
  73. 73. 
    Murphy TL, Grajales-Reyes GE, Wu X, Tussiwand R, Briseno CG et al. 2016. Transcriptional control of dendritic cell development. Annu. Rev. Immunol. 34:93–119
    [Google Scholar]
  74. 74. 
    Schonheit J, Kuhl C, Gebhardt ML, Klett FF, Riemke P et al. 2013. PU.1 level-directed chromatin structure remodeling at the Irf8 gene drives dendritic cell commitment. Cell Rep 3:1617–28
    [Google Scholar]
  75. 75. 
    Durai V, Bagadia P, Granja JM, Satpathy AT, Kulkarni DH et al. 2019. Cryptic activation of an Irf8 enhancer governs cDC1 fate specification. Nat. Immunol. 20:1161–73
    [Google Scholar]
  76. 76. 
    Bagadia P, Huang X, Liu TT, Durai V, Grajales-Reyes GE et al. 2019. An Nfil3-Zeb2-Id2 pathway imposes Irf8 enhancer switching during cDC1 development. Nat. Immunol. 20:1174–85
    [Google Scholar]
  77. 77. 
    Wang P, Xue Y, Han Y, Lin L, Wu C et al. 2014. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science 344:310–13
    [Google Scholar]
  78. 78. 
    Steinman RM, Hawiger D, Nussenzweig MC. 2003. Tolerogenic dendritic cells. Annu. Rev. Immunol. 21:685–711
    [Google Scholar]
  79. 79. 
    Zhang M, Tang H, Guo Z, An H, Zhu X et al. 2004. Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat. Immunol. 5:1124–33
    [Google Scholar]
  80. 80. 
    Huang Y, Min S, Lui Y, Sun J, Su X et al. 2012. Global mapping of H3K4me3 and H3K27me3 reveals chromatin state-based regulation of human monocyte-derived dendritic cells in different environments. Genes Immun 13:311–20
    [Google Scholar]
  81. 81. 
    Cichocki F, Miller JS, Anderson SK, Bryceson YT. 2013. Epigenetic regulation of NK cell differentiation and effector functions. Front. Immunol. 4:55
    [Google Scholar]
  82. 82. 
    Nandakumar V, Chou Y, Zang L, Huang XF, Chen SY. 2013. Epigenetic control of natural killer cell maturation by histone H2A deubiquitinase, MYSM1. PNAS 110:E3927–36
    [Google Scholar]
  83. 83. 
    Victor AR, Weigel C, Scoville SD, Chan WK, Chatman K et al. 2018. Epigenetic and posttranscriptional regulation of CD16 expression during human NK cell development. J. Immunol. 200:565–72
    [Google Scholar]
  84. 84. 
    Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo JP et al. 2018. Innate lymphoid cells: 10 years on. Cell 174:1054–66
    [Google Scholar]
  85. 85. 
    Cherrier DE, Serafini N, Di Santo JP. 2018. Innate lymphoid cell development: a T cell perspective. Immunity 48:1091–103
    [Google Scholar]
  86. 86. 
    Koues OI, Collins PL, Cella M, Robinette ML, Porter SI et al. 2016. Distinct gene regulatory pathways for human innate versus adaptive lymphoid cells. Cell 165:1134–46
    [Google Scholar]
  87. 87. 
    Stadhouders R, Li BWS, de Bruijn MJW, Gomez A, Rao TN et al. 2018. Epigenome analysis links gene regulatory elements in group 2 innate lymphocytes to asthma susceptibility. J. Allergy Clin. Immunol. 142:1793–807
    [Google Scholar]
  88. 88. 
    Liu B, Yang L, Zhu X, Li H, Zhu P et al. 2019. Yeats4 drives ILC lineage commitment via activation of Lmo4 transcription. J. Exp. Med. 216:2653–68
    [Google Scholar]
  89. 89. 
    Antignano F, Braam M, Hughes MR, Chenery AL, Burrows K et al. 2016. G9a regulates group 2 innate lymphoid cell development by repressing the group 3 innate lymphoid cell program. J. Exp. Med. 213:1153–62
    [Google Scholar]
  90. 90. 
    Bal SM, Golebski K, Spits H. 2020. Plasticity of innate lymphoid cell subsets. Nat. Rev. Immunol. 20:9552–65
    [Google Scholar]
  91. 91. 
    Mowel WK, McCright SJ, Kotzin JJ, Collet MA, Uyar A et al. 2017. Group 1 innate lymphoid cell lineage identity is determined by a cis-regulatory element marked by a long non-coding RNA. Immunity 47:435–49.e8
    [Google Scholar]
  92. 92. 
    Ohne Y, Silver JS, Thompson-Snipes L, Collet MA, Blanck JP et al. 2016. IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity. Nat. Immunol. 17:646–55
    [Google Scholar]
  93. 93. 
    Liu B, Ye B, Yang L, Zhu X, Huang G et al. 2017. Long noncoding RNA lncKdm2b is required for ILC3 maintenance by initiation of Zfp292 expression. Nat. Immunol 18:499–508
    [Google Scholar]
  94. 94. 
    Qi X, Qiu J, Chang J, Ji Y, Yang Q et al. 2021. Brg1 restrains the pro-inflammatory properties of ILC3s and modulates intestinal immunity. Mucosal Immunol 14:38–52 https://doi.org/10.1038/s41385-020-0317-3. Erratum. 2021. Mucosal Immunol 14:277 https://doi.org/10.1038/s41385-020-0324-4
    [Crossref] [Google Scholar]
  95. 95. 
    Austenaa L, Barozzi I, Chronowska A, Termanini A, Ostuni R et al. 2012. The histone methyltransferase Wbp7 controls macrophage function through GPI glycolipid anchor synthesis. Immunity 36:572–85
    [Google Scholar]
  96. 96. 
    Liu Y, Zhang Q, Ding Y, Li X, Zhao D et al. 2015. Histone lysine methyltransferase Ezh1 promotes TLR-triggered inflammatory cytokine production by suppressing Tollip. J. Immunol. 194:2838–46
    [Google Scholar]
  97. 97. 
    Zhang X, Wang Y, Yuan J, Li N, Pei S et al. 2018. Macrophage/microglial Ezh2 facilitates autoimmune inflammation through inhibition of Socs3. J. Exp. Med. 215:1365–82
    [Google Scholar]
  98. 98. 
    Zhao D, Zhang Q, Liu Y, Li X, Zhao K et al. 2016. H3K4me3 demethylase Kdm5a is required for NK cell activation by associating with p50 to suppress SOCS1. Cell Rep 15:288–99
    [Google Scholar]
  99. 99. 
    Han D, Liu J, Chen C, Dong L, Liu Y et al. 2019. Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells. Nature 566:270–74
    [Google Scholar]
  100. 100. 
    Wang H, Hu X, Huang M, Liu J, Gu Y et al. 2019. Mettl3-mediated mRNA m6A methylation promotes dendritic cell activation. Nature Commun 10:1898
    [Google Scholar]
  101. 101. 
    Wang L, Wen M, Cao X. 2019. Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses. Science 365:6454eaav0758
    [Google Scholar]
  102. 102. 
    Li T, Diner BA, Chen J, Cristea IM. 2012. Acetylation modulates cellular distribution and DNA sensing ability of interferon-inducible protein IFI16. PNAS 109:10558–63
    [Google Scholar]
  103. 103. 
    Xia P, Ye B, Wang S, Zhu X, Du Y et al. 2016. Glutamylation of the DNA sensor cGAS regulates its binding and synthase activity in antiviral immunity. Nat. Immunol. 17:369–78
    [Google Scholar]
  104. 104. 
    Li X, Zhang Q, Ding Y, Liu Y, Zhao D et al. 2016. Methyltransferase Dnmt3a upregulates HDAC9 to deacetylate the kinase TBK1 for activation of antiviral innate immunity. Nat. Immunol. 17:806–15
    [Google Scholar]
  105. 105. 
    Chen L, Fischle W, Verdin E, Greene WC. 2001. Duration of nuclear NF-κB action regulated by reversible acetylation. Science 293:1653–57
    [Google Scholar]
  106. 106. 
    Lu T, Jackson MW, Wang B, Yang M, Chance MR et al. 2010. Regulation of NF-κB by NSD1/FBXL11-dependent reversible lysine methylation of p65. PNAS 107:46–51
    [Google Scholar]
  107. 107. 
    Villarino AV, Kanno Y, O'Shea JJ 2017. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat. Immunol. 18:374–84
    [Google Scholar]
  108. 108. 
    Chen K, Liu J, Liu S, Xia M, Zhang X et al. 2017. Methyltransferase SETD2-mediated methylation of STAT1 is critical for interferon antiviral activity. Cell 170:492–506.e14
    [Google Scholar]
  109. 109. 
    Wang C, Wang Q, Xu X, Xie B, Zhao Y et al. 2017. The methyltransferase NSD3 promotes antiviral innate immunity via direct lysine methylation of IRF3. J. Exp. Med. 214:3597–610
    [Google Scholar]
  110. 110. 
    Chiang JJ, Sparrer KMJ, van Gent M, Lassig C, Huang T et al. 2018. Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity. Nat. Immunol. 19:53–62
    [Google Scholar]
  111. 111. 
    Chen YG, Kim MV, Chen X, Batista PJ, Aoyama S et al. 2017. Sensing self and foreign circular RNAs by intron identity. Mol. Cell 67:228–38.e5
    [Google Scholar]
  112. 112. 
    Lin H, Jiang M, Liu L, Yang Z, Ma Z et al. 2019. The long noncoding RNA Lnczc3h7a promotes a TRIM25-mediated RIG-I antiviral innate immune response. Nat. Immunol. 20:812–23
    [Google Scholar]
  113. 113. 
    Jiang M, Zhang S, Yang Z, Lin H, Zhu J et al. 2018. Self-recognition of an inducible host lncRNA by RIG-I feedback restricts innate immune response. Cell 173:906–19.e13
    [Google Scholar]
  114. 114. 
    Xie Q, Chen S, Tian R, Huang X, Deng R et al. 2018. Long noncoding RNA ITPRIP-1 positively regulates the innate immune response through promotion of oligomerization and activation of MDA5. J. Virol. 92:17e00507–18
    [Google Scholar]
  115. 115. 
    Zhang P, Cao L, Zhou R, Yang X, Wu M. 2019. The lncRNA Neat1 promotes activation of inflammasomes in macrophages. Nat. Commun. 10:1495
    [Google Scholar]
  116. 116. 
    Zhou Y, Li M, Xue Y, Li Z, Wen W et al. 2019. Interferon-inducible cytoplasmic lncLrrc55-AS promotes antiviral innate responses by strengthening IRF3 phosphorylation. Cell Res 29:641–54
    [Google Scholar]
  117. 117. 
    Aznaourova M, Janga H, Sefried S, Kaufmann A, Dorna J et al. 2020. Noncoding RNA MaIL1 is an integral component of the TLR4-TRIF pathway. PNAS 117:9042–53
    [Google Scholar]
  118. 118. 
    Liu CX, Li X, Nan F, Jiang S, Gao X et al. 2019. Structure and degradation of circular RNAs regulate PKR activation in innate immunity. Cell 177:865–80.e21
    [Google Scholar]
  119. 119. 
    Smale ST, Tarakhovsky A, Natoli G. 2014. Chromatin contributions to the regulation of innate immunity. Annu. Rev. Immunol. 32:489–511
    [Google Scholar]
  120. 120. 
    Hargreaves DC, Horng T, Medzhitov R. 2009. Control of inducible gene expression by signal-dependent transcriptional elongation. Cell 138:129–45
    [Google Scholar]
  121. 121. 
    Zhou Q, Zhang Y, Wang B, Zhou W, Bi Y et al. 2020. KDM2B promotes IL-6 production and inflammatory responses through Brg1-mediated chromatin remodeling. Cell Mol. Immunol. 17:8834–42
    [Google Scholar]
  122. 122. 
    Liu X, Lu Y, Zhu J, Liu M, Xie M et al. 2019. A long noncoding RNA, antisense IL-7, promotes inflammatory gene transcription through facilitating histone acetylation and switch/sucrose nonfermentable chromatin remodeling. J. Immunol. 203:1548–59
    [Google Scholar]
  123. 123. 
    Tartey S, Matsushita K, Vandenbon A, Ori D, Imamura T et al. 2014. Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex. EMBO J 33:2332–48
    [Google Scholar]
  124. 124. 
    Iwafuchi-Doi M, Zaret KS. 2016. Cell fate control by pioneer transcription factors. Development 143:1833–37
    [Google Scholar]
  125. 125. 
    Jin J, Hu H, Li HS, Yu J, Xiao Y et al. 2014. Noncanonical NF-κB pathway controls the production of type I interferons in antiviral innate immunity. Immunity 40:342–54
    [Google Scholar]
  126. 126. 
    Zhu Y, van Essen D, Saccani S. 2012. Cell-type-specific control of enhancer activity by H3K9 trimeth-ylation. Mol. Cell 46:408–23
    [Google Scholar]
  127. 127. 
    van Essen D, Zhu Y, Saccani S. 2010. A feed-forward circuit controlling inducible NF-κB target gene activation by promoter histone demethylation. Mol. Cell 39:750–60
    [Google Scholar]
  128. 128. 
    Stender JD, Pascual G, Liu W, Kaikkonen MU, Do K et al. 2012. Control of proinflammatory gene programs by regulated trimethylation and demethylation of histone H4K20. Mol. Cell 48:28–38
    [Google Scholar]
  129. 129. 
    Zhou W, Zhu P, Wang J, Pascual G, Ohgi KA et al. 2008. Histone H2A monoubiquitination represses transcription by inhibiting RNA polymerase II transcriptional elongation. Mol. Cell 29:69–80
    [Google Scholar]
  130. 130. 
    Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K et al. 2012. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 488:404–8
    [Google Scholar]
  131. 131. 
    Li X, Zhang Q, Shi Q, Liu Y, Zhao K et al. 2017. Demethylase Kdm6a epigenetically promotes IL-6 and IFN-β production in macrophages. J. Autoimmun. 80:85–94
    [Google Scholar]
  132. 132. 
    Cribbs A, Hookway ES, Wells G, Lindow M, Obad S et al. 2018. Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of natural killer cells. J. Biol. Chem. 293:2422–37
    [Google Scholar]
  133. 133. 
    Atianand MK, Hu W, Satpathy AT, Shen Y, Ricci EP et al. 2016. A long noncoding RNA lincRNA-EPS acts as a transcriptional brake to restrain inflammation. Cell 165:1672–85
    [Google Scholar]
  134. 134. 
    Xu J, Xu X, Wang B, Ma Y, Zhang L et al. 2017. Nuclear carbonic anhydrase 6B associates with PRMT5 to epigenetically promote IL-12 expression in innate response. PNAS 114:8620–25
    [Google Scholar]
  135. 135. 
    Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S et al. 2010. Suppression of inflammation by a synthetic histone mimic. Nature 468:1119–23
    [Google Scholar]
  136. 136. 
    Xue S, Liu C, Sun X, Li W, Zhang C et al. 2016. TET3 inhibits type I IFN production independent of DNA demethylation. Cell Rep 16:1096–105
    [Google Scholar]
  137. 137. 
    Sadler AJ, Suliman BA, Yu L, Yuan X, Wang D et al. 2015. The acetyltransferase HAT1 moderates the NF-κB response by regulating the transcription factor PLZF. Nat. Commun. 6:6795
    [Google Scholar]
  138. 138. 
    Shakespear MR, Halili MA, Irvine KM, Fairlie DP, Sweet MJ. 2011. Histone deacetylases as regulators of inflammation and immunity. Trends Immunol 32:335–43
    [Google Scholar]
  139. 139. 
    Zhang Q, Zhao K, Shen Q, Han Y, Gu Y et al. 2015. Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature 525:389–93
    [Google Scholar]
  140. 140. 
    Kayama H, Ramirez-Carrozzi VR, Yamamoto M, Mizutani T, Kuwata H et al. 2008. Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IκBζ. J. Biol. Chem. 283:12468–77
    [Google Scholar]
  141. 141. 
    Carson WF 4th, Cavassani KA, Soares EM, Hirai S, Kittan NA et al. 2017. The STAT4/MLL1 epigenetic axis regulates the antimicrobial functions of murine macrophages. J. Immunol. 199:1865–74
    [Google Scholar]
  142. 142. 
    Chen X, Liu X, Zhang Y, Huai W, Zhou Q et al. 2020. Methyltransferase Dot1l preferentially promotes innate IL-6 and IFN-β production by mediating H3K79me2/3 methylation in macrophages. Cell Mol. Immunol. 17:76–84
    [Google Scholar]
  143. 143. 
    Saccani S, Pantano S, Natoli G. 2002. p38-Dependent marking of inflammatory genes for increased NF-κB recruitment. Nat. Immunol. 3:69–75
    [Google Scholar]
  144. 144. 
    Yamamoto Y, Verma UN, Prajapati S, Kwak YT, Gaynor RB. 2003. Histone H3 phosphorylation by IKK-α is critical for cytokine-induced gene expression. Nature 423:655–59
    [Google Scholar]
  145. 145. 
    Anest V, Hanson JL, Cogswell PC, Steinbrecher KA, Strahl BD, Baldwin AS. 2003. A nucleosomal function for IκB kinase-α in NF-κB-dependent gene expression. Nature 423:659–63
    [Google Scholar]
  146. 146. 
    Carpenter S, Aiello D, Atianand MK, Ricci EP, Gandhi P et al. 2013. A long noncoding RNA mediates both activation and repression of immune response genes. Science 341:789–92
    [Google Scholar]
  147. 147. 
    Hah N, Benner C, Chong LW, Yu RT, Downes M, Evans RM. 2015. Inflammation-sensitive super enhancers form domains of coordinately regulated enhancer RNAs. PNAS 112:E297–302
    [Google Scholar]
  148. 148. 
    Xia M, Liu J, Wu X, Liu S, Li G et al. 2013. Histone methyltransferase Ash1l suppresses interleukin-6 production and inflammatory autoimmune diseases by inducing the ubiquitin-editing enzyme A20. Immunity 39:470–81
    [Google Scholar]
  149. 149. 
    Wei H, Wang B, Miyagi M, She Y, Gopalan B et al. 2013. PRMT5 dimethylates R30 of the p65 subunit to activate NF-κB. PNAS 110:13516–21
    [Google Scholar]
  150. 150. 
    Reintjes A, Fuchs JE, Kremser L, Lindner HH, Liedl KR et al. 2016. Asymmetric arginine dimethylation of RelA provides a repressive mark to modulate TNFα/NF-κB response. PNAS 113:4326–31
    [Google Scholar]
  151. 151. 
    Kawahara TL, Michishita E, Adler AS, Damian M, Berber E et al. 2009. SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell 136:62–74
    [Google Scholar]
  152. 152. 
    Gilchrist M, Thorsson V, Li B, Rust AG, Korb M et al. 2006. Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 441:173–78
    [Google Scholar]
  153. 153. 
    Jiang S, Yan W, Wang SE, Baltimore D. 2019. Dual mechanisms of posttranscriptional regulation of Tet2 by Let-7 microRNA in macrophages. PNAS 116:12416–21
    [Google Scholar]
  154. 154. 
    Winkler R, Gillis E, Lasman L, Safra M, Geula S et al. 2019. m6A modification controls the innate immune response to infection by targeting type I interferons. Nat. Immunol. 20:173–82
    [Google Scholar]
  155. 155. 
    Netea MG, Quintin J, van der Meer JW. 2011. Trained immunity: a memory for innate host defense. Cell Host Microbe 9:355–61
    [Google Scholar]
  156. 156. 
    Arase H, Mocarski ES, Campbell AE, Hill AB, Lanier LL. 2002. Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296:1323–26
    [Google Scholar]
  157. 157. 
    Hammer Q, Ruckert T, Borst EM, Dunst J, Haubner A et al. 2018. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells. Nat. Immunol. 19:453–63
    [Google Scholar]
  158. 158. 
    Weizman OE, Song E, Adams NM, Hildreth AD, Riggan L et al. 2019. Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12. Nat. Immunol. 20:1004–11
    [Google Scholar]
  159. 159. 
    Foster SL, Hargreaves DC, Medzhitov R. 2007. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447:972–78
    [Google Scholar]
  160. 160. 
    Beeson PB. 1947. Tolerance to bacterial pyrogens: I. Factors influencing its development. J. Exp. Med. 86:29–38
    [Google Scholar]
  161. 161. 
    Yan Q, Carmody RJ, Qu Z, Ruan Q, Jager J et al. 2012. Nuclear factor-κB binding motifs specify Toll-like receptor-induced gene repression through an inducible repressosome. PNAS 109:14140–45
    [Google Scholar]
  162. 162. 
    Chen X, El Gazzar M, Yoza BK, McCall CE 2009. The NF-κB factor RelB and histone H3 lysine methyltransferase G9a directly interact to generate epigenetic silencing in endotoxin tolerance. J. Biol. Chem. 284:27857–65
    [Google Scholar]
  163. 163. 
    El Gazzar M, Yoza BK, Chen X, Hu J, Hawkins GA, McCall CE. 2008. G9a and HP1 couple histone and DNA methylation to TNFα transcription silencing during endotoxin tolerance. J. Biol. Chem. 283:32198–208
    [Google Scholar]
  164. 164. 
    Seeley JJ, Baker RG, Mohamed G, Bruns T, Hayden MS et al. 2018. Induction of innate immune memory via microRNA targeting of chromatin remodelling factors. Nature 559:114–19
    [Google Scholar]
  165. 165. 
    Novakovic B, Habibi E, Wang SY, Arts RJW, Davar R et al. 2016. β-Glucan reverses the epigenetic state of LPS-induced immunological tolerance. Cell 167:1354–68.e14
    [Google Scholar]
  166. 166. 
    Dominguez-Andres J, Novakovic B, Li Y, Scicluna BP, Gresnigt MS et al. 2019. The itaconate pathway is a central regulatory node linking innate immune tolerance and trained immunity. Cell Metab 29:211–20.e5
    [Google Scholar]
  167. 167. 
    Schliehe C, Flynn EK, Vilagos B, Richson U, Swaminanthan S et al. 2015. The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection. Nat. Immunol. 16:67–74
    [Google Scholar]
  168. 168. 
    Aegerter H, Kulikauskaite J, Crotta S, Patel H, Kelly G et al. 2020. Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection. Nature Immunol 21:145–57
    [Google Scholar]
  169. 169. 
    Cooper MA, Elliott JM, Keyel PA, Yang L, Carrero JA, Yokoyama WM. 2009. Cytokine-induced memory-like natural killer cells. PNAS 106:1915–19
    [Google Scholar]
  170. 170. 
    Luetke-Eversloh M, Hammer Q, Durek P, Nordstrom K, Gasparoni G et al. 2014. Human cytomegalovirus drives epigenetic imprinting of the IFNG locus in NKG2Chi natural killer cells. PLOS Pathog 10:e1004441
    [Google Scholar]
  171. 171. 
    Lau CM, Adams NM, Geary CD, Weizman OE, Rapp M et al. 2018. Epigenetic control of innate and adaptive immune memory. Nat. Immunol. 19:963–72
    [Google Scholar]
  172. 172. 
    Gamliel M, Goldman-Wohl D, Isaacson B, Gur C, Stein N et al. 2018. Trained memory of human uterine NK cells enhances their function in subsequent pregnancies. Immunity 48:951–62.e5
    [Google Scholar]
  173. 173. 
    Park SH, Park-Min KH, Chen J, Hu X, Ivashkiv LB. 2011. Tumor necrosis factor induces GSK3 kinase-mediated cross-tolerance to endotoxin in macrophages. Nat. Immunol. 12:607–15
    [Google Scholar]
  174. 174. 
    Park SH, Kang K, Giannopoulou E, Qiao Y, Kim G et al. 2017. Type I interferons and the cytokine TNF cooperatively reprogram the macrophage epigenome to promote inflammatory activation. Nat. Immunol. 18:1104–16
    [Google Scholar]
  175. 175. 
    Chen J, Ivashkiv LB. 2010. IFN-γ abrogates endotoxin tolerance by facilitating Toll-like receptor-induced chromatin remodeling. PNAS 107:19438–43
    [Google Scholar]
  176. 176. 
    Qiao Y, Giannopoulou EG, Chan CH, Park SH, Gong S et al. 2013. Synergistic activation of inflammatory cytokine genes by interferon-γ-induced chromatin remodeling and Toll-like receptor signaling. Immunity 39:454–69
    [Google Scholar]
  177. 177. 
    Kang K, Bachu M, Park SH, Bae S, Park-Min KH, Ivashkiv LB. 2019. IFN-γ selectively suppresses a subset of TLR4-activated genes and enhancers to potentiate macrophage activation. Nat. Commun. 10:3320
    [Google Scholar]
  178. 178. 
    Yao Y, Jeyanathan M, Haddadi S, Barra NG, Vaseghi-Shanjani M et al. 2018. Induction of autonomous memory alveolar macrophages requires T cell help and is critical to trained immunity. Cell 175:1634–50.e17
    [Google Scholar]
  179. 179. 
    Weber GF, Chousterman BG, He S, Fenn AM, Nairz M et al. 2015. Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis. Science 347:1260–65
    [Google Scholar]
  180. 180. 
    Shen Q, Zhang Q, Shi Y, Shi Q, Jiang Y et al. 2018. Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation. Nature 554:123–27
    [Google Scholar]
  181. 181. 
    de Laval B, Maurizio J, Kandalla PK, Brisou G, Simmonet L et al. 2020. C/EBPβ-dependent epigenetic memory induces trained immunity in hematopoietic stem cells. Cell Stem Cell 26:657–74.e8 Erratum. 2020. Cell Stem Cell 26:793
    [Google Scholar]
  182. 182. 
    Quintin J, Saeed S, Martens JHA, Giamarellos-Bourboulis EJ, Ifrim DC et al. 2012. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe 12:223–32
    [Google Scholar]
  183. 183. 
    Saeed S, Quintin J, Kerstens HH, Rao NA, Aghajanirefah A et al. 2014. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science 345:1251086
    [Google Scholar]
  184. 184. 
    Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC et al. 2012. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. PNAS 109:17537–42
    [Google Scholar]
  185. 185. 
    Kaufmann E, Sanz J, Dunn JL, Khan N, Mendonca LE et al. 2018. BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell 172:176–90.e19
    [Google Scholar]
  186. 186. 
    Fanucchi S, Fok ET, Dalla E, Shibayama Y, Borner K et al. 2019. Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments. Nat. Genet. 51:138–50
    [Google Scholar]
  187. 187. 
    Arts RJ, Novakovic B, Ter Horst R, Carvalho A, Bekkering S et al. 2016. Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity. Cell Metab 24:807–19
    [Google Scholar]
  188. 188. 
    Bekkering S, Arts RJW, Novakovic B, Kourtzelis I, van der Heijden C et al. 2018. Metabolic induction of trained immunity through the mevalonate pathway. Cell 172:135–46.e9
    [Google Scholar]
  189. 189. 
    Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S et al. 2014. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345:1250684
    [Google Scholar]
  190. 190. 
    Owen OE, Kalhan SC, Hanson RW. 2002. The key role of anaplerosis and cataplerosis for citric acid cycle function. J. Biol. Chem. 277:30409–12
    [Google Scholar]
  191. 191. 
    Becker PB, Horz W. 2002. ATP-dependent nucleosome remodeling. Annu. Rev. Biochem. 71:247–73
    [Google Scholar]
  192. 192. 
    Martin JL, McMillan FM. 2002. SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold. Curr. Opin. Struct. Biol. 12:783–93
    [Google Scholar]
  193. 193. 
    Trefely S, Lovell CD, Snyder NW, Wellen KE. 2020. Compartmentalised acyl-CoA metabolism and roles in chromatin regulation. Mol. Metab. 38:100941
    [Google Scholar]
  194. 194. 
    Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR et al. 2004. Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 23:2369–80
    [Google Scholar]
  195. 195. 
    Misawa T, Takahama M, Kozaki T, Lee H, Zou J et al. 2013. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat. Immunol. 14:454–60
    [Google Scholar]
  196. 196. 
    Teperino R, Schoonjans K, Auwerx J. 2010. Histone methyl transferases and demethylases: Can they link metabolism and transcription?. Cell Metab. 12:4321–27
    [Google Scholar]
  197. 197. 
    Liu PS, Wang H, Li X, Chao T, Teav T et al. 2017. α-Ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat. Immunol. 18:985–94
    [Google Scholar]
  198. 198. 
    Wang P, Xu J, Wang Y, Cao X. 2017. An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism. Science 358:1051–55
    [Google Scholar]
  199. 199. 
    Covarrubias AJ, Aksoylar HI, Yu J, Snyder NW, Worth AJ et al. 2016. Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation. eLife 5:e11612
    [Google Scholar]
  200. 200. 
    Lauterbach MA, Hanke JE, Serefidou M, Mangan MSJ, Kolbe CC et al. 2019. Toll-like receptor signaling rewires macrophage metabolism and promotes histone acetylation via ATP-citrate lyase. Immunity 51:997–1011.e7
    [Google Scholar]
  201. 201. 
    Yu W, Wang Z, Zhang K, Chi Z, Xu T et al. 2019. One-carbon metabolism supports S-adenosylmethionine and histone methylation to drive inflammatory macrophages. Mol. Cell 75:1147–60.e5
    [Google Scholar]
  202. 202. 
    Langston PK, Nambu A, Jung J, Shibata M, Aksoylar HI et al. 2019. Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses. Nat. Immunol. 20:1186–95
    [Google Scholar]
  203. 203. 
    Sutendra G, Kinnaird A, Dromparis P, Paulin R, Stenson TH et al. 2014. A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation. Cell 158:84–97
    [Google Scholar]
  204. 204. 
    Zhang D, Tang Z, Huang H, Zhou G, Cui C et al. 2019. Metabolic regulation of gene expression by histone lactylation. Nature 574:575–80
    [Google Scholar]
  205. 205. 
    Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF et al. 2013. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496:238–42
    [Google Scholar]
  206. 206. 
    Mills EL, Kelly B, Logan A, Costa ASH, Varma M et al. 2016. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 167:457–70.e13
    [Google Scholar]
  207. 207. 
    Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D et al. 2018. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 556:113–17
    [Google Scholar]
  208. 208. 
    Bambouskova M, Gorvel L, Lampropoulou V, Sergushichev A, Loginicheva E et al. 2018. Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis. Nature 556:501–4
    [Google Scholar]
  209. 209. 
    Hardbower DM, Asim M, Luis PB, Singh K, Barry DP et al. 2017. Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications. PNAS 114:E751–60
    [Google Scholar]
  210. 210. 
    Xiao M, Yang H, Xu W, Ma S, Lin H et al. 2012. Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev 26:1326–38
    [Google Scholar]
  211. 211. 
    Chang PV, Hao L, Offermanns S, Medzhitov R. 2014. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. PNAS 111:2247–52
    [Google Scholar]
  212. 212. 
    Schulthess J, Pandey S, Capitani M, Rue-Albrecht KC, Arnold I et al. 2019. The short chain fatty acid butyrate imprints an antimicrobial program in macrophages. Immunity 50:432–45.e7
    [Google Scholar]
  213. 213. 
    Fellows R, Denizot J, Stellato C, Cuomo A, Jain P et al. 2018. Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. Nat. Commun. 9:1105
    [Google Scholar]
  214. 214. 
    Heim CE, Bosch ME, Yamada JK, Aldrich AL, Chaudhari SS et al. 2020. Lactate production by Staphylococcus aureus biofilm inhibits HDAC11 to reprogramme the host immune response during persistent infection. . Nat. Microbiol. 5:101271–84
    [Google Scholar]
  215. 215. 
    Wu S-E, Hashimoto-Hill S, Woo V, Eshleman EM, Whitt J et al. 2020. Microbiota-derived metabolite promotes HDAC3 activity in the gut. . Nature 586:108–12
    [Google Scholar]
  216. 216. 
    Chakraborty AA, Laukka T, Myllykoski M, Ringel AE, Booker MA et al. 2019. Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate. Science 363:1217–22
    [Google Scholar]
  217. 217. 
    Xiao H, Jedrychowski MP, Schweppe DK, Huttlin EL, Yu Q et al. 2020. A quantitative tissue-specific landscape of protein redox regulation during aging. Cell 180:968–83.e24
    [Google Scholar]
  218. 218. 
    Liu J, Zhang X, Chen K, Cheng Y, Liu S et al. 2019. CCR7 chemokine receptor-inducible lnc-Dpf3 restrains dendritic cell migration by inhibiting HIF-1α-mediated glycolysis. Immunity 50:600–15.e15
    [Google Scholar]
  219. 219. 
    Liu Y, You Y, Lu Z, Yang J, Li P et al. 2019. N6-Methyladenosine RNA modification-mediated cellular metabolism rewiring inhibits viral replication. Science 365:1171–76
    [Google Scholar]
/content/journals/10.1146/annurev-immunol-093019-123619
Loading
/content/journals/10.1146/annurev-immunol-093019-123619
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error