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MicroRNA in immunity and autoimmunity

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Abstract

MicroRNAs (miRNAs) are about 20–22 nucleotide conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3′-untranslated region of specific messenger RNAs (mRNAs) for degradation or translational repression. During the last two decades, miRNAs have emerged as criticalregulators of a range of biological processes including immune cell lineage commitment, differentiation, maturation, and immune signaling pathways. The endoribonucleases such as Dicer, which is required for miRNA biogenesis, has also been shown to play an important role in inflammatory response and autoimmunity. Thus, dysregulated miRNA expression patterns have been documented in a broad range of human diseases including inflammatory and autoimmune diseases. In this review, we will discuss recent advances in miRNAs mediated regulation of inflammatory responses and autoimmune pathogenesis. Specifically, we will discuss how miRNAs regulate autoimmunity through affecting the development, differentiation, and function of various cell types such as innate immune cells, adaptive immune cells and local resident cells. The identification of distinct miRNA expression patterns, and a comprehensive understanding of the roles of those dysregulated miRNAs in inflammatory autoimmune pathogenesis offers inspirations of not only potential molecular diagnostic markers but also novel therapeutic strategies for treating inflammatory autoimmune diseases.

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References

  1. Lee RC, Feinbaum RL, Ambros V (1993) The C-elegans heterochronic gene Lin-4 encodes small RNAs with antisense complementarity to Lin-14. Cell 75:843–854

    Article  PubMed  CAS  Google Scholar 

  2. Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene Lin-14 by Lin-4 mediates temporal pattern-formation in C-elegans. Cell 75:855–862

    Article  PubMed  CAS  Google Scholar 

  3. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20

    Article  PubMed  CAS  Google Scholar 

  4. Griffiths-Jones S (2004) The microRNA registry. Nucleic Acids Res 32:D109–D111

    Article  PubMed  CAS  Google Scholar 

  5. Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B, Rigoutsos I (2006) A pattern-based method for the identification of microRNA binding sites and their corresponding heteroduplexes. Cell 126:1203–1217

    Article  PubMed  CAS  Google Scholar 

  6. O’Connell RM, Rao DS, Baltimore D (2012) microRNA regulation of inflammatory responses. Annu Rev Immunol 30:295–312

    Google Scholar 

  7. Li H, Xie H, Liu W, Hu R, Huang B, Tan YF, Xu K, Sheng ZF, Zhou HD, Wu XP et al (2010) A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans (vol 119, pg 3666, 2009). J Clin Invest 120:395–395

    Article  CAS  Google Scholar 

  8. Luo XB, Yang WL, Ye DQ, Cui HJ, Zhang Y, Hirankarn N, Qian XX, Tang YJ, Lau YL, de Vries N et al (2011) A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus. Plos Genet 7

  9. Baulcombe D (2004) RNA silencing in plants. Nature 431:356–363

    Article  PubMed  CAS  Google Scholar 

  10. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811

    Article  PubMed  CAS  Google Scholar 

  11. Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappa B-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 103:12481–12486

    Article  PubMed  CAS  Google Scholar 

  12. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14:1902–1910

    Article  PubMed  CAS  Google Scholar 

  13. Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6:376–385

    Article  PubMed  CAS  Google Scholar 

  14. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP (2008) The impact of microRNAs on protein output. Nature 455:64–U38

    Article  PubMed  CAS  Google Scholar 

  15. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N (2008) Widespread changes in protein synthesis induced by microRNAs. Nature 455:58–63

    Article  PubMed  CAS  Google Scholar 

  16. Vasudevan S, Tong YC, Steitz JA (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318:1931–1934

    Article  PubMed  CAS  Google Scholar 

  17. Kim DH, Saetrom P, Snove O, Rossi JJ (2008) MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc Natl Acad Sci U S A 105:16230–16235

    Article  PubMed  CAS  Google Scholar 

  18. O’Carroll D, Mecklenbrauker I, Das PP, Santana A, Koenig U, Enright AJ, Miska EA, Tarakhovsky A (2007) A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev 21:1999–2004

    Article  PubMed  Google Scholar 

  19. Cobb BS, Nesterova TB, Thompson E, Hertweck A, O’Connor E, Godwin J, Wilson CB, Brockdorff N, Fisher AG, Smale ST et al (2005) T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J Exp Med 201:1367–1373

    Article  PubMed  CAS  Google Scholar 

  20. Muljo SA, Ansel KM, Kanellopoulou C, Livingston DM, Rao A, Rajewsky K (2005) Aberrant T cell differentiation in the absence of Dicer. J Exp Med 202:261–269

    Article  PubMed  CAS  Google Scholar 

  21. Koralov SB, Muljo SA, Galler GR, Krek A, Chakraborty T, Kanellopoulou C, Jensen K, Cobb BS, Merkenschlager M, Rajewsky N et al (2008) Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell 132:860–874

    Article  PubMed  CAS  Google Scholar 

  22. Chong MM, Rasmussen JP, Rudensky AY, Littman DR (2008) The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease. J Exp Med 205:2005–2017

    Article  PubMed  CAS  Google Scholar 

  23. Liston A, Lu LF, O’Carroll D, Tarakhovsky A, Rudensky AY (2008) Dicer-dependent microRNA pathway safeguards regulatory T cell function. J Exp Med 205:1993–2004

    Article  PubMed  CAS  Google Scholar 

  24. Biton M, Levin A, Slyper M, Alkalay I, Horwitz E, Mor H, Kredo-Russo S, Avnit-Sagi T, Cojocaru G, Zreik F et al (2011) Epithelial microRNAs regulate gut mucosal immunity via epithelium-T cell crosstalk. Nat Immunol 12:239–246

    Google Scholar 

  25. Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD (2008) MicroRNAs: new regulators of immune cell development and function. Nat Immunol 9:839–845

    Article  PubMed  CAS  Google Scholar 

  26. O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D (2010) Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol 10:111–122

    Google Scholar 

  27. Dai R, Ahmed SA (2011) MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Transl Res 157:163–179

    Google Scholar 

  28. Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, Bozzoni I (2005) A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell 123:819–831

    Article  PubMed  CAS  Google Scholar 

  29. Velu CS, Baktula AM, Grimes HL (2009) Gfi1 regulates miR-21 and miR-196b to control myelopoiesis. Blood 113:4720–4728

    Article  PubMed  CAS  Google Scholar 

  30. Hock H, Hamblen MJ, Rooke HM, Traver D, Bronson RT, Cameron S, Orkin SH (2003) Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation. Immunity 18:109–120

    Article  PubMed  CAS  Google Scholar 

  31. O’Connell RM, Chaudhuri AA, Rao DS, Baltimore D (2009) Inositol phosphatase SHIP1 is a primary target of miR-155. Proc Natl Acad Sci U S A 106:7113–7118

    Article  PubMed  Google Scholar 

  32. Johnnidis JB, Harris MH, Wheeler RT, Stehling-Sun S, Lam MH, Kirak O, Brummelkamp TR, Fleming MD, Camargo FD (2008) Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 451:1125–1129

    Article  PubMed  CAS  Google Scholar 

  33. Fedeli M, Napolitano A, Wong MP, Marcais A, de Lalla C, Colucci F, Merkenschlager M, Dellabona P, Casorati G (2009) Dicer-dependent microRNA pathway controls invariant NKT cell development. J Immunol 183:2506–2512

    Article  PubMed  CAS  Google Scholar 

  34. Zhou L, Seo KH, He HZ, Pacholczyk R, Meng DM, Li CG, Xu J, She JX, Dong Z, Mi QS (2009) Tie2cre-induced inactivation of the miRNA-processing enzyme Dicer disrupts invariant NKT cell development. Proc Natl Acad Sci U S A 106:10266–10271

    Article  PubMed  CAS  Google Scholar 

  35. Fontana L, Pelosi E, Greco P, Racanicchi S, Testa U, Liuzzi F, Croce CM, Brunetti E, Grignani F, Peschle C (2007) MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation. Nat Cell Biol 9:775–U790

    Article  PubMed  CAS  Google Scholar 

  36. Rosa A, Ballarino M, Sorrentino A, Sthandier O, De Angelis FG, Marchioni M, Masella B, Guarini A, Fatica A, Peschle C et al (2007) The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation. Proc Natl Acad Sci U S A 104:19849–19854

    Article  PubMed  CAS  Google Scholar 

  37. Martinez-Nunez RT, Louafi F, Friedmann PS, Sanchez-Elsner T (2009) MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by down-regulation of DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN). J Biol Chem 284:16334–16342

    Article  PubMed  CAS  Google Scholar 

  38. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA et al (2007) Requirement of bic/microRNA-155 for normal immune function. Science 316:608–611

    Article  PubMed  CAS  Google Scholar 

  39. O’Connell RM, Taganov KD, Boldin MP, Cheng GH, Baltimore D (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A 104:1604–1609

    Article  PubMed  Google Scholar 

  40. Gatto G, Rossi A, Rossi D, Kroening S, Bonatti S, Mallardo M (2008) Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappa B pathway. Nucleic Acids Res 36:6608–6619

    Article  PubMed  CAS  Google Scholar 

  41. Yin QY, Wang X, McBride J, Fewell C, Flemington E (2008) B-cell receptor activation induces BIC/miR-155 expression through a conserved AP-1 element. J Biol Chem 283:2654–2662

    Article  PubMed  CAS  Google Scholar 

  42. Androulidaki A, Iliopoulos D, Arranz A, Doxaki C, Schworer S, Zacharioudaki V, Margioris AN, Tsichlis PN, Tsatsanis C (2009) The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity 31:220–231

    Article  PubMed  CAS  Google Scholar 

  43. Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O’Leary JJ, Ruan QG, Johnson DS, Chen YH, O’Neill LAJ (2010) Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol 11:141–U159

    Article  PubMed  CAS  Google Scholar 

  44. Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, Fabbri M, Alder H, Liu CG, Calin GA et al (2007) Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 179:5082–5089

    PubMed  CAS  Google Scholar 

  45. Iliopoulos D, Hirsch HA, Struhl K (2009) An epigenetic switch involving NF-kappa B, Lin28, Let-7 microRNA, and IL6 links inflammation to cell transformation. Cell 139:693–706

    Article  PubMed  CAS  Google Scholar 

  46. Bauernfeind F, Rieger A, Hornung V (2012) NLRP3 inflammasome activity is negatively controlled by miR-223. Immunology 137:292–292

    Google Scholar 

  47. Bauernfeind F, Rieger A, Schildberg FA, Knolle PA, Schmid-Burgk JL, Hornung V (2012) NLRP3 Inflammasome activity is negatively controlled by miR-223. J Immunol 189:4175–4181

    Google Scholar 

  48. Haneklaus M, Gerlic M, Kurowska-Stolarska M, Rainey AA, Pich D, McInnes IB, Hammerschmidt W, O’Neill LA, Masters SL (2012) Cutting edge: miR-223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1beta production. J Immunol 189:3795–3799

    Google Scholar 

  49. Tang YJ, Luo XB, Cui HJ, Ni XM, Yuan M, Guo YZ, Huang XF, Zhou HB, de Vries N, Tak PP et al (2009) MicroRNA-146a contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum 60:1065–1075

    Article  PubMed  CAS  Google Scholar 

  50. Pauley KM, Stewart CM, Gauna AE, Dupre LC, Kuklani R, Chan AL, Pauley BA, Reeves WH, Chan EKL, Cha S (2011) Altered miR-146a expression in Sjogren’s syndrome and its functional role in innate immunity. Eur J Immunol 41:2029–2039

    Article  PubMed  CAS  Google Scholar 

  51. Li QJ, Chau J, Ebert PJR, Sylvester G, Min H, Liu G, Braich R, Manoharan M, Soutschek J, Skare P et al (2007) miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129:147–161

    Article  PubMed  CAS  Google Scholar 

  52. Ebert PJR, Jiang S, Xie JM, Li QJ, Davis MM (2009) An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a. Nat Immunol 10:1162–U1144

    Article  PubMed  CAS  Google Scholar 

  53. Xiao CC, Srinivasan L, Calado DP, Patterson HC, Zhang BC, Wang J, Henderson JM, Kutok JL, Rajewsky K (2008) Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9:405–414

    Article  PubMed  CAS  Google Scholar 

  54. Thai TH, Calado DP, Casola S, Ansel KM, Xiao CC, Xue YZ, Murphy A, Frendewey D, Valenzuela D, Kutok JL et al (2007) Regulation of the germinal center response by microRNA-155. Science 316:604–608

    Article  PubMed  CAS  Google Scholar 

  55. Steiner DF, Thomas MF, Hu JK, Yang Z, Babiarz JE, Allen CD, Matloubian M, Blelloch R, Ansel KM (2011) MicroRNA-29 regulates T-box transcription factors and interferon-gamma production in helper T cells. Immunity 35:169–181

    Article  PubMed  CAS  Google Scholar 

  56. Smith KM, Guerau-de-Arellano M, Costinean S, Williams JL, Bottoni A, Mavrikis Cox G, Satoskar AR, Croce CM, Racke MK, Lovett-Racke AE et al (2012) miR-29ab1 deficiency identifies a negative feedback loop controlling Th1 bias that is dysregulated in multiple sclerosis. J Immunol 189:1567–1576

    Article  PubMed  CAS  Google Scholar 

  57. Ma F, Xu S, Liu XG, Zhang Q, Xu XF, Liu MF, Hua MM, Li N, Yao HP, Cao XT (2011) The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-gamma. Nat Immunol 12:861–U865

    Article  PubMed  CAS  Google Scholar 

  58. Du CS, Liu C, Kang JH, Zhao GX, Ye ZQ, Huang SC, Li ZX, Wu ZY, Pei G (2010) MicroRNA miR-326 regulates T-H-17 differentiation and is associated with the pathogenesis of multiple sclerosis (vol 10, pg 1252, 2009). Nat Immunol 11:543–543

    Article  CAS  Google Scholar 

  59. Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B, Dent AL, Craft J, Crotty S (2009) Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325:1006–1010

    Article  PubMed  CAS  Google Scholar 

  60. Yu D, Rao S, Tsai LM, Lee SK, He YQ, Sutcliffe EL, Srivastava M, Linterman M, Zheng L, Simpson N et al (2009) The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31:457–468

    Article  PubMed  CAS  Google Scholar 

  61. Takahashi H, Kanno T, Nakayamada S, Hirahara K, Sciume G, Muljo SA, Kuchen S, Casellas R, Wei L, Kanno Y et al (2012) TGF-beta and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells. Nat Immunol 13:587–595

    Article  PubMed  CAS  Google Scholar 

  62. Stittrich AB, Haftmann C, Sgouroudis E, Kuhl AA, Hegazy AN, Panse I, Riedel R, Flossdorf M, Dong J, Fuhrmann F et al (2010) The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes. Nat Immunol 11:1057–U1111

    Article  PubMed  CAS  Google Scholar 

  63. Jindra PT, Bagley J, Godwin JG, Iacomini J (2010) Costimulation-dependent expression of microRNA-214 increases the ability of T cells to proliferate by targeting Pten. J Immunol 185:990–997

    Article  PubMed  CAS  Google Scholar 

  64. Zhou XY, Jeker LT, Fife BT, Zhu S, Anderson MS, McManus MT, Bluestone JA (2008) Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med 205:1983–1991

    Article  PubMed  CAS  Google Scholar 

  65. Boldin MP, Taganov KD, Rao DS, Yang LL, Zhao JL, Kalwani M, Garcia-Flores Y, Luong M, Devrekanli A, Xu J et al (2011) miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med 208:1189–1201

    Article  PubMed  CAS  Google Scholar 

  66. Lu LF, Boldin MP, Chaudhry A, Lin LL, Taganov KD, Hanada T, Yoshimura A, Baltimore D, Rudensky AY (2010) Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell 142:914–929

    Article  PubMed  CAS  Google Scholar 

  67. Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, Tanaka K, Loeb GB, Lee H, Yoshimura A, Rajewsky K et al (2009) Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity 30:80–91

    Article  PubMed  CAS  Google Scholar 

  68. Huang B, Zhao J, Lei Z, Shen SQ, Li D, Shen GX, Zhang GM, Feng ZH (2009) miR-142-3p restricts cAMP production in CD4(+)CD25(−) T cells and CD4(+)CD25(+) T-REG cells by targeting AC9 mRNA. Embo Rep 10:180–185

    Article  PubMed  CAS  Google Scholar 

  69. Monticelli S, Ansel KM, Xiao CC, Socci ND, Krichevsky AM, Thai TH, Rajewsky N, Marks DS, Sander C, Rajewsky K et al (2005) MicroRNA profiling of the murine hematopoietic system. Genome Biol 6

  70. Xiao CC, Calado DP, Galler G, Thai TH, Patterson HC, Wang J, Rajewsky N, Bender TP, Rajewsky K (2007) MiR-150 controls B cell differentiation by targeting the transcription factor c-myb. Cell 131:146–159

    Article  PubMed  CAS  Google Scholar 

  71. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR et al (2008) Targeted deletion reveals essential and overlapping functions of the miR-17 similar to 92 family of miRNA clusters. Cell 132:875–886

    Article  PubMed  CAS  Google Scholar 

  72. Zhou BY, Wang S, Mayr C, Bartel DP, Lodish HF (2008) miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely (vol 104, pg 7080, 2007). Proc Natl Acad Sci U S A 105:18070–18070

    Article  CAS  Google Scholar 

  73. Vigorito E, Perks KL, Abreu-Goodger C, Bunting S, Xiang Z, Kohlhaas S, Das PP, Miska EA, Rodriguez A, Bradley A et al (2007) MicroRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity 27:847–859

    Article  PubMed  CAS  Google Scholar 

  74. Lindberg RLP, Hoffmann F, Mehling M, Kuhle J, Kappos L (2010) Altered expression of miR-17-5p in CD4(+) lymphocytes of relapsing-remitting multiple sclerosis patients. Eur J Immunol 40:888–898

    Article  PubMed  CAS  Google Scholar 

  75. Cox MB, Cairns MJ, Gandhi KS, Carroll AP, Moscovis S, Stewart GJ, Broadley S, Scott RJ, Booth DR, Lechner-Scott J et al (2010) MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood. PLoS One 5

  76. Giuseppe D, Manuela F, Andrea B, Luisa C, Rosaria TM, Massimiliano C, Barbara Z, Enrico F, Riccardo G, Massimo N et al (2010) Altered miRNA expression in T regulatory cells in course of multiple sclerosis. J Neuroimmunol 228:137–138

    Google Scholar 

  77. Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EKL (2008) Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther 10

  78. Kurowska-Stolarska M, Alivernini S, Ballantine LE, Asquith DL, Millar NL, Gilchrist DS, Reilly J, Ierna M, Fraser AR, Stolarski B et al (2011) MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci U S A 108:11193–11198

    Article  PubMed  CAS  Google Scholar 

  79. Pan W, Zhu S, Yuan M, Cui HJ, Wang LJ, Luo XB, Li J, Zhou HB, Tang YJ, Shen N (2010) MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4(+) T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol 184:6773–6781

    Article  PubMed  CAS  Google Scholar 

  80. Zhao X, Tang YJ, Qu B, Cui HJ, Wang SJ, Wang LJ, Luo XB, Huang XF, Li J, Chen SL et al (2010) MicroRNA-125a contributes to elevated inflammatory chemokine RANTES levels via targeting KLF13 in systemic lupus erythematosus. Arthritis Rheum 62:3425–3435

    Article  PubMed  CAS  Google Scholar 

  81. Rouas R, Fawad-Kazan H, El Zein N, Lewalle P, Rothe F, Simion A, Akl H, Mourtada M, El Rifai M, Burny A et al (2009) Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression. Eur J Immunol 39:1608–1618

    Article  PubMed  CAS  Google Scholar 

  82. Oertli M, Engler DB, Kohler E, Koch M, Meyer TF, Muller A (2011) MicroRNA-155 is essential for the T cell-mediated control of Helicobacter pylori infection and for the induction of chronic gastritis and colitis. J Immunol 187:3578–3586

    Article  PubMed  CAS  Google Scholar 

  83. Hezova R, Slaby O, Faltejskova P, Mikulkova Z, Buresova I, Raja KRM, Hodek J, Ovesna J, Michalek J (2010) microRNA-342, microRNA-191 and microRNA-510 are differentially expressed in T regulatory cells of type 1 diabetic patients. Cell Immunol 260:70–74

    Article  PubMed  CAS  Google Scholar 

  84. Balasubramanyam M, Aravind S, Gokulakrishnan K, Prabu P, Sathishkumar C, Ranjani H, Mohan V (2011) Impaired miR-146a expression links subclinical inflammation and insulin resistance in type 2 diabetes. Mol Cell Biochem 351:197–205

    Article  PubMed  CAS  Google Scholar 

  85. Sonkoly E, Janson P, Majuri ML, Savinko T, Fyhrquist N, Eidsmo L, Xu N, Meisgen F, Wei TL, Bradley M et al (2010) MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte-associated antigen 4. J Allergy Clin Immunol 126:581–U306

    Article  PubMed  CAS  Google Scholar 

  86. Zhu S, Pan W, Song XY, Liu Y, Shao XR, Tang YJ, Liang D, He DY, Wang HL, Liu WJ et al (2012) The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-alpha. Nat Med 18:1077-+

    PubMed  CAS  Google Scholar 

  87. Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL (2011) MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-alpha-PU.1 pathway. Nat Med 17:64–70

    Article  PubMed  CAS  Google Scholar 

  88. Junker A, Krumbholz M, Eisele S, Mohan H, Augstein F, Bittner R, Lassmann H, Wekerle H, Hohlfeld R, Meinl E (2009) MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 132:3342–3352

    Article  PubMed  Google Scholar 

  89. Stanczyk J, Pedrioli DAL, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, Detmar M, Gay S, Kyburz D (2008) Altered expression of microRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum 58:1001–1009

    Article  PubMed  Google Scholar 

  90. Bluml S, Bonelli M, Niederreiter B, Puchner A, Mayr G, Hayer S, Koenders MI, van den Berg WB, Smolen J, Redlich K (2011) Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum 63:1281–1288

    Article  PubMed  Google Scholar 

  91. Nakasa T, Shibuya H, Nagata Y, Niimoto T, Ochi M (2011) The inhibitory effect of microRNA-146a expression on bone destruction in collagen-induced arthritis. Arthritis Rheum 63:1582–1590

    Article  PubMed  CAS  Google Scholar 

  92. Alsaleh G, Suffert G, Semaan N, Juncker T, Frenzel L, Gottenberg JE, Sibilia J, Pfeffer S, Wachsmann D (2009) Bruton’s tyrosine kinase is involved in miR-346-related regulation of IL-18 release by lipopolysaccharide-activated rheumatoid fibroblast-like synoviocytes. J Immunol 182:5088–5097

    Article  PubMed  CAS  Google Scholar 

  93. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, Saura R, Kurosaka M, Kumagai S (2009) MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheum 60:1294–1304

    Article  PubMed  Google Scholar 

  94. Papadopoulou AS, Dooley J, Linterman MA, Pierson W, Ucar O, Kyewski B, Zuklys S, Hollander GA, Matthys P, Gray DH et al (2012) The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-alpha receptor. Nat Immunol 13:181–187

    Article  CAS  Google Scholar 

  95. Wang G, Kwan BCH, Lai FMM, Chow KM, Li PKT, Szeto CC (2011) Elevated levels of miR-146a and miR-155 in kidney biopsy and urine from patients with IgA nephropathy. Dis Markers 30:171–179

    Article  PubMed  Google Scholar 

  96. Madhan T, Dirk K, Robert HG, Michael H, Hans-Juergen T, Klaus ZU (2010) Detection and quantification of microRNA expression in human peripheral blood microvesicles from multiple sclerosis patients treated with interferon-beta-1b. J Neuroimmunol 228:9–9

    Google Scholar 

  97. O’Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA, Kahn ME, Rao DS, Baltimore D (2010) MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity 33:607–619

    Article  PubMed  Google Scholar 

  98. Du CS, Liu C, Kang JH, Zhao GX, Ye ZQ, Huang SC, Li ZX, Wu ZY, Pei G (2009) MicroRNA miR-326 regulates T-H-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 10:1252–U1254

    Article  PubMed  CAS  Google Scholar 

  99. Jopling CL (2010) Targeting microRNA-122 to treat hepatitis C virus infection. Viruses-Basel 2:1382–1393

    Article  CAS  Google Scholar 

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Acknowledgments

We apologize to the many authors whose work could not be cited directly because of space limitations. This work was supported by grants from 973 programs (No. 2013CB944904 and No. 2010CB529705) and National Natural Science Foundation of China (No. 30930084, No. 81230075 and No. 91029708).

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Authors and Affiliations

  1. The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Shu Zhu, Wen Pan & Youcun Qian

  2. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520, USA

    Shu Zhu

  3. Department of Genetics, Yale University School of Medicine, New Haven, CT, 06520, USA

    Wen Pan

  4. Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, 06520, USA

    Wen Pan

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  1. Shu Zhu
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  2. Wen Pan
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  3. Youcun Qian
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Correspondence to Shu Zhu or Youcun Qian.

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Zhu, S., Pan, W. & Qian, Y. MicroRNA in immunity and autoimmunity. J Mol Med 91, 1039–1050 (2013). https://doi.org/10.1007/s00109-013-1043-z

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  • DOI: https://doi.org/10.1007/s00109-013-1043-z

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