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Gordino G, Costa-Pereira S, Corredeira P, et al. MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2. EMBO Rep. 2021;23(1):e52234doi: 10.15252/embr.202052234.
Gordino, G., Costa-Pereira, S., Corredeira, P., Alves, P., Costa, L., Gomes, A. Q., Silva-Santos, B., & Ribot, J. C. (2022). MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2. EMBO reports, 23(1), e52234. https://doi.org/10.15252/embr.202052234
Gordino, Gisela, et al. "MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2." EMBO reports vol. 23,1 (2022): e52234. doi: https://doi.org/10.15252/embr.202052234
Gordino G, Costa-Pereira S, Corredeira P, Alves P, Costa L, Gomes AQ, Silva-Santos B, Ribot JC. MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2. EMBO Rep. 2022 Jan 05;23(1):e52234. doi: 10.15252/embr.202052234. Epub 2021 Nov 24. PMID: 34821000.
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EMBO Rep. 2022 Jan 05;23(1):e52234. doi: 10.15252/embr.202052234. Epub 2021 Nov 24.

MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2.

EMBO reports

Gisela Gordino, Sara Costa-Pereira, Patrícia Corredeira, Patrícia Alves, Luís Costa, Anita Q Gomes, Bruno Silva-Santos, Julie C Ribot

Affiliations

  1. Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
  2. Medical Oncology Division, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
  3. Escola Superior de Tecnologia da Saúde de Lisboa, Lisbon, Portugal.

PMID: 34821000 DOI: 10.15252/embr.202052234

Abstract

γδ T cells are a conserved population of lymphocytes that contributes to anti-tumor responses through its overt type 1 inflammatory and cytotoxic properties. We have previously shown that human γδ T cells acquire this profile upon stimulation with IL-2 or IL-15, in a differentiation process dependent on MAPK/ERK signaling. Here, we identify microRNA-181a as a key modulator of human γδ T cell differentiation. We observe that miR-181a is highly expressed in patients with prostate cancer and that this pattern associates with lower expression of NKG2D, a critical mediator of cancer surveillance. Interestingly, miR-181a expression negatively correlates with an activated type 1 effector profile obtained from in vitro differentiated γδ T cells and miR-181a overexpression restricts their levels of NKG2D and TNF-α. Upon in silico analysis, we identify two miR-181a candidate targets, Map3k2 and Notch2, which we validate via overexpression coupled with luciferase assays. These results reveal a novel role for miR-181a as critical regulator of human γδ T cell differentiation and highlight its potential for manipulation of γδ T cells in next-generation immunotherapies.

© 2021 The Authors. Published under the terms of the CC BY 4.0 license.

Keywords: cancer; effector T lymphocytes; miR-181a; microRNAs; γδ T cells

References

  1. Amado T, Amorim A, Enguita FJ, Romero PV, Inácio D, de Miranda MP, Winter SJ, Simas JP, Krueger A, Schmolka N et al (2020) MicroRNA-181a regulates IFN-γ expression in effector CD8+ T cell differentiation. J Mol Med 98: 309-320 - PubMed
  2. Ambros V (2004) The functions of animal microRNAs. Nature 431: 350-355 - PubMed
  3. Amsen D, Antov A, Jankovic D, Sher A, Radtke F, Souabni A, Busslinger M, McCright B, Gridley T, Flavell RA (2007) Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch. Immunity 27: 89-99 - PubMed
  4. Amsen D, Helbig C, Backer RA (2015) Notch in T cell differentiation: all things considered. Trends Immunol 36: 802-814 - PubMed
  5. Argentati K, Re F, Serresi S, Tucci MG, Bartozzi B, Bernardini G, Provinciali M (2003) Reduced number and impaired function of circulating gamma delta T cells in patients with cutaneous primary melanoma. J Invest Dermatol 120: 829-834 - PubMed
  6. Batlle E, Massagué J (2019) Transforming growth factor-β signaling in immunity and cancer. Immunity 50: 924-940 - PubMed
  7. Berard M, Tough DF (2002) Qualitative differences between naïve and memory T cells. Immunology 106: 127-138 - PubMed
  8. Bland CL, Byrne-Hoffman CN, Fernandez A, Rellick SL, Deng W, Klinke 2nd DJ (2018) Exosomes derived from B16F0 melanoma cells alter the transcriptome of cytotoxic T cells that impacts mitochondrial respiration. FEBS J 285: 1033-1050 - PubMed
  9. Blume J, Zur Lage S, Witzlau K, Georgiev H, Weiss S, Łyszkiewicz M, Ziȩtara N, Krueger A (2016) Overexpression of Vα14Jα18 TCR promotes development of iNKT cells in the absence of miR-181a/b-1. Immunol Cell Biol 94: 741-746 - PubMed
  10. Bonneau E, Neveu B, Kostantin E, Tsongalis GJ, De Guire V (2019) How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market. EJIFCC 30: 114-127 - PubMed
  11. Bryant NL, Suarez-Cuervo C, Gillespie GY, Markert JM, Nabors LB, Meleth S, Lopez RD, Lamb Jr LS (2009) Characterization and immunotherapeutic potential of gammadelta T-cells in patients with glioblastoma. Neuro Oncol 11: 357-367 - PubMed
  12. Chang X, Liu F, Wang X, Lin A, Zhao H, Su B (2011) The kinases MEKK2 and MEKK3 regulate transforming growth factor-β-mediated helper T cell differentiation. Immunity 34: 201-212 - PubMed
  13. Clark AR, Dean JL, Saklatvala J (2003) Post-transcriptional regulation of gene expression by mitogen-activated protein kinase p38. FEBS Lett 546: 37-44 - PubMed
  14. Correia DV, Lopes A, Silva-Santos B (2013) Tumor cell recognition by γδ T lymphocytes: T-cell receptor vs. NK-cell receptors. Oncoimmunology 2: e22892 - PubMed
  15. DeBarros A, Chaves-Ferreira M, d'Orey F, Ribot JC, Silva-Santos B (2011) CD70-CD27 interactions provide survival and proliferative signals that regulate T cell receptor-driven activation of human γδ peripheral blood lymphocytes. Eur J Immunol 41: 195-201 - PubMed
  16. Dieli F, Poccia F, Lipp M, Sireci G, Caccamo N, Di Sano C, Salerno A (2003) Differentiation of effector/memory Vdelta2 T cells and migratory routes in lymph nodes or inflammatory sites. J Exp Med 198: 391-397 - PubMed
  17. Duval F, Mathieu M, Labrecque N (2015) Notch controls effector CD8+ T cell differentiation. Oncotarget 6: 21787-21788 - PubMed
  18. Fiala GJ, Gomes AQ, Silva-Santos B (2020) From thymus to periphery: molecular basis of effector γδ-T cell differentiation. Immunol Rev 298: 47-60 - PubMed
  19. Fichtner AS, Ravens S, Prinz I (2020) Human γδ TCR repertoires in health and disease. Cells 9: 800 - PubMed
  20. Fragoso R, Mao T, Wang S, Schaffert S, Gong X, Yue S, Luong R, Min H, Yashiro-Ohtani Y, Davis M et al (2012) Modulating the strength and threshold of NOTCH oncogenic signals by mir-181a-1/b-1. PLoS Genet 8: e1002855 - PubMed
  21. Gaafar A, Aljurf MD, Al-Sulaiman A, Iqniebi A, Manogaran PS, Mohamed GE, Al-Sayed A, Alzahrani H, Alsharif F, Mohareb F et al (2009) Defective gammadelta T-cell function and granzyme B gene polymorphism in a cohort of newly diagnosed breast cancer patients. Exp Hematol 37: 838-848 - PubMed
  22. Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, Nair VS, Xu Y, Khuong A, Hoang CD et al (2015) The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med 21: 938-945 - PubMed
  23. Giaimo BD, Oswald F, Borggrefe T (2017) Dynamic chromatin regulation at Notch target genes. Transcription 8: 61-66 - PubMed
  24. Gibbons DL, Haque SF, Silberzahn T, Hamilton K, Langford C, Ellis P, Carr R, Hayday AC (2009) Neonates harbour highly active gammadelta T cells with selective impairments in preterm infants. Eur J Immunol 39: 1794-1806 - PubMed
  25. Gogoi D, Dar AA, Chiplunkar SV (2014) Involvement of Notch in activation and effector functions of γδ T cells. J Immunol 192: 2054-2062 - PubMed
  26. Gomes AQ, Martins DS, Silva-Santos B (2010) Targeting γδ T lymphocytes for cancer immunotherapy: From novel mechanistic insight to clinical application. Cancer Res 70: 10024-10027 - PubMed
  27. Gonnermann D, Oberg HH, Kellner C, Peipp M, Sebens S, Kabelitz D et al (2015) Resistance of cyclooxygenase-2 expressing pancreatic ductal adenocarcinoma cells against γδ T cell cytotoxicity. Oncoimmunology 4: e988460 - PubMed
  28. Hao J, Dong S, Xia S, He W, Jia H, Zhang S, Wei J, O’Brien RL, Born WK, Wu Z et al (2011) Regulatory role of Vγ1 γδ T cells in tumor immunity through IL-4 production. J Immunol 187: 4979-4986 - PubMed
  29. Huber M, Lohoff M (2014) IRF4 at the crossroads of effector T-cell fate decision. Eur J Immunol 44: 1886-1895 - PubMed
  30. Jazdzewski K, Liyanarachchi S, Swierniak M, Pachucki J, Ringel MD, Jarzab B, de la Chapelle A (2009) Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc Natl Acad Sci USA 106: 1502-1505 - PubMed
  31. Jurberg AD, Vasconcelos-Fontes L, Cotta-de-Almeida V (2015) A tale from TGF-β superfamily for thymus ontogeny and function. Front Immunol 6: 442 - PubMed
  32. Kirigin FF, Lindstedt K, Sellars M, Ciofani M, Low SL, Jones L, Bell F, Pauli F, Bonneau R, Myers RM et al (2012) Dynamic microRNA gene transcription and processing during T cell development. J Immunol 188: 3257-3267 - PubMed
  33. Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42: D68-D73 - PubMed
  34. Kozomara A, Birgaoanu M, Griffiths-Jones S (2019) miRBase: from microRNA sequences to function. Nucleic Acids Res 47: D155-D162 - PubMed
  35. Kuroda H, Saito H, Ikeguchi M (2012) Decreased number and reduced NKG2D expression of Vδ1 γδ T cells are involved in the impaired function of Vδ1 γδ T cells in the tissue of gastric cancer. Gastric Cancer 15: 433-439 - PubMed
  36. Lança T, Correia DV, Moita CF, Raquel H, Neves-Costa A, Ferreira C, Ramalho JS, Barata JT, Moita LF, Gomes AQ et al (2010) The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia/lymphoma susceptibility to gammadelta T-cell cytotoxicity. Blood 115: 2407-2411 - PubMed
  37. Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Ørum H (2009) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327: 198-201 - PubMed
  38. Lee CW, Wohlan K, Dallmann I, Förster R, Ganser A, Krueger A, Scherr M, Eder M, Koenecke C (2016) miR-181a expression in donor T cells modulates graft-versus-host disease after allogeneic bone marrow transplantation. J Immunol 196: 3927-3934 - PubMed
  39. Lemus-Diaz N, Böker KO, Rodriguez-Polo I, Mitter M, Preis J, Arlt M, Gruber J (2017) Dissecting miRNA gene repression on single cell level with an advanced fluorescent reporter system. Sci Rep 7: 45197 - PubMed
  40. Li Q-J, 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 - PubMed
  41. Li H, Luo K, Pauza CD (2008) TNF-α is a positive regulatory factor for human Vγ2Vδ2 T cells. J Immunol 181: 7131-7137 - PubMed
  42. Li BO, Wang XI, Choi IY, Wang Y-C, Liu S, Pham AT, Moon H, Smith DJ, Rao DS, Boldin MP et al (2017) miR-146a modulates autoreactive Th17 cell differentiation and regulates organ-specific autoimmunity. J Clin Invest 127: 3702-3716 - PubMed
  43. Lo Presti E, Pizzolato G, Gulotta E, Cocorullo G, Gulotta G, Dieli F, Meraviglia S (2017) Current advances in γδ T cell-based tumor immunotherapy. Front Immunol 8: 1401 - PubMed
  44. Ma C, Zhang Q, Ye J, Wang F, Zhang Y, Wevers E, Schwartz T, Hunborg P, Varvares MA, Hoft DF et al (2012) Tumor-infiltrating γδ T lymphocytes predict clinical outcome in human breast cancer. J Immunol 189: 5029-5036 - PubMed
  45. Maekawa Y, Minato Y, Ishifune C, Kurihara T, Kitamura A, Kojima H, Yagita H, Sakata-Yanagimoto M, Saito T, Taniuchi I et al (2008) Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity. Nat Immunol 9: 1140-1147 - PubMed
  46. Marten A, von Lilienfeld-Toal M, Buchler W, Schmidt J (2006) Soluble MIC is elevated in the serum of patients with pancreatic carcinoma diminishing gammadelta T cell cytotoxicity. Int J Cancer 119: 2359-2365 - PubMed
  47. Misono S, Seki N, Mizuno K, Yamada Y, Uchida A, Arai T, Kumamoto T, Sanada H, Suetsugu T, Inoue H (2018) Dual strands of the miR-145 duplex (miR-145-5p and miR-145-3p) regulate oncogenes in lung adenocarcinoma pathogenesis. J Hum Genet 63: 1015-1028 - PubMed
  48. Mitra R, Sun J, Zhao Z (2015) microRNA regulation in cancer: one arm or two arms? Int J Cancer 137: 1516-1518 - PubMed
  49. Mitra R, Adams CM, Jiang W, Greenawalt E, Eischen CM (2020) Pan-cancer analysis reveals cooperativity of both strands of microRNA that regulate tumorigenesis and patient survival. Nat Commun 11: 968 - PubMed
  50. Neilson JR, Zheng GXY, Burge CB, Sharp PA (2007) Dynamic regulation of miRNA expression in ordered stages of cellular development. Genes Dev 21: 578-589 - PubMed
  51. O'Shea JJ, Lahesmaa R, Vahedi G, Laurence A, Kanno Y (2011) Genomic views of STAT function in CD4+ T helper cell differentiation. Nat Rev Immunol 11: 239-250 - PubMed
  52. Peng G, Wang HY, Peng W, Kiniwa Y, Seo KH, Wang RF (2007) Tumor-infiltrating gammadelta T cells suppress T and dendritic cell function via mechanisms controlled by a unique toll-like receptor signaling pathway. Immunity 27: 334-348 - PubMed
  53. Pink RC, Samuel P, Massa D, Caley DP, Brooks SA, Carter DR (2015) The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance in ovarian cancer cells. Gynecol Oncol 137: 143-151 - PubMed
  54. Pons-Espinal M, de Luca E, Marzi MJ, Beckervordersandforth R, Armirotti A, Nicassio F, Fabel K, Kempermann G, De Pietri TD (2017) Synergic functions of miRNAs determine neuronal fate of adult neural stem cells. Stem Cell Reports 8: 1046-1061 - PubMed
  55. Rei M, Gonçalves-Sousa N, Lança T, Thompson RG, Mensurado S, Balkwill FR, Kulbe H, Pennington DJ, Silva-Santos B (2014) Murine CD27(-) Vγ6(+) γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages. Proc Natl Acad Sci USA 111: E3562-E3570 - PubMed
  56. Ribot JC, deBarros A, Pang DJ, Neves JF, Peperzak V, Roberts SJ, Girardi M, Borst J, Hayday AC, Pennington DJ et al (2009) CD27 is a thymic determinant of the balance between interferon-gamma- and interleukin 17-producing gammadelta T cell subsets. Nat Immunol 10: 427-436 - PubMed
  57. Ribot JC, Ribeiro ST, Correia DV, Sousa AE, Silva-Santos B (2014) Human γδ thymocytes are functionally immature and differentiate into cytotoxic type 1 effector T cells upon IL-2/IL-15 signaling. J Immunol 192: 2237-2243 - PubMed
  58. Rose SA, Wroblewska A, Dhainaut M, Yoshida H, Shaffer JM, Bektesevic A, Ben-Zvi B, Rhoads A, Kim EY, Yu B et al (2021) A microRNA expression and regulatory element activity atlas of the mouse immune system. Nat Immunol 22: 914-927 - PubMed
  59. Rozenberg JM, Taylor JM, Mack CP (2018) RBPJ binds to consensus and methylated cis elements within phased nucleosomes and controls gene expression in human aortic smooth muscle cells in cooperation with SRF. Nucleic Acids Res 46: 8232-8244 - PubMed
  60. Sandrock I, Ziętara N, Łyszkiewicz M, Oberdörfer L, Witzlau K, Krueger A, Prinz I (2015) MicroRNA-181a/b-1 is not required for innate γδ NKT effector cell development. PLoS One 10: e0145010 - PubMed
  61. Sang W, Zhang C, Zhang D, Wang Y, Sun C, Niu M, Sun X, Zhou C, Zeng L, Pan B et al (2015) MicroRNA-181a, a potential diagnosis marker, alleviates acute graft versus host disease by regulating IFN-γ production. Am J Hematol 90: 998-1007 - PubMed
  62. Schmeck B, Beermann W, van Laak V, Zahlten J, Opitz B, Witzenrath M, Hocke AC, Chakraborty T, Kracht M, Rosseau S et al (2005) Intracellular bacteria differentially regulated endothelial cytokine release by MAPK-dependent histone modification. J Immunol 175: 2843-2850 - PubMed
  63. Schmolka N, Papotto PH, Romero PV, Amado T, Enguita FJ, Amorim A, Rodrigues AF, Gordon KE, Coroadinha AS, Boldin M et al (2018) MicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1. Sci Immunol 3: eaao1392 - PubMed
  64. Silva-Santos B, Serre K, Norell H (2015) γδ T cells in cancer. Nat Rev Immunol 15: 683-691 - PubMed
  65. Silva-Santos B, Mensurado S, Coffelt SB (2019) γδ T cells: pleiotropic immune effectors with therapeutic potential in cancer. Nat Rev Cancer 19: 392-404 - PubMed
  66. Sivori S, Vacca P, Del Zotto G, Munari E, Mingari MC, Moretta L (2019) Human NK cells: surface receptors, inhibitory checkpoints, and translational applications. Cell Mol Immunol 16: 430-441 - PubMed
  67. Skeen MJ, Ziegler HK (1995) Activation of gamma delta T cells for production of IFN-gamma is mediated by bacteria via macrophage-derived cytokines IL-1 and IL-12. J Immunol 154: 5832-5841 - PubMed
  68. Su B, Cheng J, Yang J, Guo Z (2001) MEKK2 is required for T-cell receptor signals in JNK activation and interleukin-2 gene expression. J Biol Chem 276: 14784-14790 - PubMed
  69. Van Coppernolle S, Vanhee S, Verstichel G, Snauwaert S, van der Spek A, Velghe I, Sinnesael M, Heemskerk MH, Taghon T, Leclercq G et al (2012) Notch induces human T-cell receptor γδ+ thymocytes to differentiate along a parallel, highly proliferative and bipotent CD4 CD8 double-positive pathway. Leukemia 26: 127-138 - PubMed
  70. Wan J, Ling X, Peng B, Ding G (2018) miR-142-5p regulates CD4+ T cells in human non-small cell lung cancer through PD-L1 expression via the PTEN pathway. Oncol Rep 40: 272-282 - PubMed
  71. Winter SJ, Krueger A (2019) Development of unconventional T cells controlled by microRNA. Front Immunol 10: 2520 - PubMed
  72. Winter SJ, Kunze-Schumacher H, Imelmann E, Grewers Z, Osthues T, Krueger A (2019) MicroRNA miR-181a/b-1 controls MAIT cell development. Immunol Cell Biol 97: 190-202 - PubMed
  73. Wu P, Wu D, Ni C, Ye J, Chen W, Hu G, Wang Z, Wang C, Zhang Z, Xia W et al (2014) γδT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer. Immunity 40: 785-800 - PubMed
  74. Wu Y, Kyle-Cezar F, Woolf RT, Naceur-Lombardelli C, Owen J, Biswas D, Lorenc A, Vantourout P, Gazinska P, Grigoriadis A et al (2019) An innate-like Vδ1+ γδ T cell compartment in the human breast is associated with remission in triple-negative breast cancer. Sci Transl Med 11: eaax9364 - PubMed
  75. Ye J, Ma C, Hsueh EC, Eickhoff CS, Zhang Y, Varvares MA, Hoft DF, Peng G (2013a) Tumor-derived γδ regulatory T cells suppress innate and adaptive immunity through the induction of immunosenescence. J Immunol 190: 2403-2414 - PubMed
  76. Ye J, Ma C, Wang F, Hsueh EC, Toth K, Huang YI, Mo W, Liu S, Han B, Varvares MA et al (2013b) Specific recruitment of γδ regulatory T cells in human breast cancer. Cancer Res 73: 6137-6148 - PubMed
  77. Ye SB, Li ZL, Luo DH, Huang BJ, Chen YS, Zhang XS, Cui J, Zeng YX, Li J (2014) Tumor-derived exosomes promote tumor progression and T-cell dysfunction through the regulation of enriched exosomal microRNAs in human nasopharyngeal carcinoma. Oncotarget 5: 5439-5452 - PubMed
  78. Yoda M, Kawamata T, Paroo Z, Ye X, Iwasaki S, Liu Q, Tomari Y (2010) ATP-dependent human RISC assembly pathways. Nat Struct Mol Biol 17: 17-23 - PubMed
  79. Yurova KA, Khaziakhmatova OG, Dunets NA, Todosenko NM, Shupletsova VV, Litvinova LS (2017) Effect of cytokines (IL-2, IL-7, and IL-15) having common γ-chain of receptors on differentiation and maturation of CD4+/CD8+ T-cells in a CD45RA T-lymphocyte population in vitro. Cell Tiss Biol 11: 356-362 - PubMed
  80. Zhao E, Maj T, Kryczek I, Li W, Wu KE, Zhao L, Wei S, Crespo J, Wan S, Vatan L et al (2016) Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction. Nat Immunol 17: 95-103 - PubMed
  81. Zhu Y, Zhang S, Li Z, Wang H, Li Z, Hu YU, Chen H, Zhang X, Cui L, Zhang J et al (2017) miR-125b-5p and miR-99a-5p downregulate human γδ T-cell activation and cytotoxicity. Cell Mol Immunol 16: 112-125 - PubMed
  82. Zietara N, Lyszkiewicz M, Witzlau K, Naumann R, Hurwitz R, Langemeier J, Bohne J, Sandrock I, Ballmaier M, Weiss S et al (2013) Critical role for miR-181a/b-1 in agonist selection of invariant natural killer T cells. Proc Natl Acad Sci USA 110: 7407-7412 - PubMed

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