MicroRNA-mediated regulation of T helper cell differentiation and plasticity

Nature Reviews Immunology

Volumn 13, Issue 9, 2013, Pages 666-678

  Baumjohann, Dirk ^a   Ansel, K Mark ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTAGOMIR; DUAL SPECIFICITY PHOSPHATASE; DUAL SPECIFICITY PHOSPHATASE 5; GAMMA INTERFERON; HOUSE DUST ALLERGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR; INTERLEUKIN 4; INTERLEUKIN 5; LET 7 PROTEIN; MICRORNA; MICRORNA 126; MICRORNA 146A; MICRORNA 155; MICRORNA 29; OLIGONUCLEOTIDE; PHOSPHATIDYLINOSITOL 3 KINASE; RETINOIC ACID; SMALL UNTRANSLATED RNA; STAT1 PROTEIN; STAT4 PROTEIN; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR T BET; UNCLASSIFIED DRUG;

ASTHMA; CD4+ T LYMPHOCYTE; CELL FATE; CELL FUNCTION; CELL TYPE; CELLULAR IMMUNITY; CYTOKINE PRODUCTION; DENDRITIC CELL; DRUG DELIVERY SYSTEM; EFFECTOR CELL; GENE EXPRESSION; GENE REGULATORY NETWORK; GENE TARGETING; HELPER CELL; HOUSE DUST ALLERGY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; LUNG; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE PROLIFERATION; MEDIATOR; NATURAL KILLER T CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE SUBPOPULATION; TH1 CELL; TH17 CELL; TH2 CELL;

ANIMALS; CELL DIFFERENTIATION; CELL SURVIVAL; GENE EXPRESSION REGULATION; HUMANS; IMMUNE TOLERANCE; LYMPHOCYTE ACTIVATION; MICRORNAS; T-LYMPHOCYTES, HELPER-INDUCER;

EID: 84883162180     PISSN: 14741733     EISSN: 14741741     Source Type: Journal    
DOI: 10.1038/nri3494     Document Type: Review

References (140)

1. Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A. & Coffman, R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348-2357 (1986).
2. Zhou, L., Chong, M. M. & Littman, D. R. Plasticity of CD4+ T cell lineage differentiation. Immunity 30, 646-655 (2009).
3. Locksley, R. M. Nine lives: plasticity among T helper cell subsets. J. Exp. Med. 206, 1643-1646 (2009).
4. Murphy, K. M. & Stockinger, B. Effector T cell plasticity: flexibility in the face of changing circumstances. Nature Immunol. 11, 674-680 (2010).
5. O'Shea, J. J. & Paul, W. E. Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 327, 1098-1102 (2010).
6. Wilson, C. B., Rowell, E. & Sekimata, M. Epigenetic control of T-helper-cell differentiation. Nature Rev. Immunol. 9, 91-105 (2009).
7. Ansel, K. M., Djuretic, I., Tanasa, B. & Rao, A. Regulation of Th2 differentiation and Il4 locus accessibility. Annu. Rev. Immunol. 24, 607-656 (2006).
8. Kanno, Y., Vahedi, G., Hirahara, K., Singleton, K. & O'Shea, J. J. Transcriptional and epigenetic control of T helper cell specification: molecular mechanisms underlying commitment and plasticity. Annu. Rev. Immunol. 30, 707-731 (2012).
9. Zhu, J., Yamane, H. & Paul, W. E. Differentiation of effector CD4 T cell populations. Annu. Rev. Immunol. 28, 445-489 (2010).
10. Ansel, K. M., Lee, D. U. & Rao, A. An epigenetic view of helper T cell differentiation. Nature Immunol. 4, 616-623 (2003).
11. Bartel, D. P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233 (2009).
12. Fabian, M. R., Sonenberg, N. & Filipowicz, W. Regulation of mRNA translation and stability by microRNAs. Annu. Rev. Biochem. 79, 351-379 (2010).
13. Krol, J., Loedige, I. & Filipowicz, W. The widespread regulation of microRNA biogenesis, function and decay. Nature Rev. Genet. 11, 597-610 (2010).
14. Mendell, J. T. & Olson, E. N. MicroRNAs in stress signaling and human disease. Cell 148, 1172-1187 (2012).
15. Hoefig, K. P. & Heissmeyer, V. MicroRNAs grow up in the immune system. Curr. Opin. Immunol. 20, 281-287 (2008).
16. Ceribelli, A., Satoh, M. & Chan, E. K. MicroRNAs and autoimmunity. Curr. Opin. Immunol. 24, 686-691 (2012).
17. O'Connell, R. M., Rao, D. S., Chaudhuri, A. A. & Baltimore, D. Physiological and pathological roles for microRNAs in the immune system. Nature Rev. Immunol. 10, 111-122 (2010).
18. Nakayamada, S., Takahashi, H., Kanno, Y. & O'Shea, J. J. Helper T cell diversity and plasticity. Curr. Opin. Immunol. 24, 297-302 (2012).
19. Xiao, C. & Rajewsky, K. MicroRNA control in the immune system: basic principles. Cell 136, 26-36 (2009).
20. Belver, L., Papavasiliou, F. N. & Ramiro, A. R. MicroRNA control of lymphocyte differentiation and function. Curr. Opin. Immunol. 23, 368-373 (2011).
21. Jeker, L. T. & Bluestone, J. A. Small RNA regulators of T cell-mediated autoimmunity. J. Clin. Immunol. 30, 347-357 (2010).
22. Monticelli, S. et al. MicroRNA profiling of the murine hematopoietic system. Genome Biol. 6, R71 (2005).
23. Landgraf, P. et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401-1414 (2007).
24. Barski, A. et al. Chromatin poises miRNA-and protein-coding genes for expression. Genome Res. 19, 1742-1751 (2009).
25. Rossi, R. L. et al. Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b. Nature Immunol. 12, 796-803 (2011).
26. Kuchen, S. et al. Regulation of microRNA expression and abundance during lymphopoiesis. Immunity 32, 828-839 (2010).
27. Muljo, S. A. et al. Aberrant T cell differentiation in the absence of Dicer. J. Exp. Med. 202, 261-269 (2005). This study provides the first evidence that miRNAs are important regulators of TH cell differentiation.
28. Cobb, B. S. et al. A role for Dicer in immune regulation. J. Exp. Med. 203, 2519-2527 (2006).
29. Tian, L. et al. Loss of T cell microRNA provides systemic protection against autoimmune pathology in mice. J. Autoimmun. 38, 39-48 (2012).
30. Chong, M. M., Rasmussen, J. P., Rudensky, A. Y. & Littman, D. R. The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease. J. Exp. Med. 205, 2005-2017 (2008).
31. Steiner, D. F. et al. MicroRNA-29 regulates T-box transcription factors and interferon production in helper T cells. Immunity 35, 169-181 (2011).
32. Bronevetsky, Y. et al. T cell activation induces proteasomal degradation of Argonaute and rapid remodeling of the microRNA repertoire. J. Exp. Med. 210, 417-432 (2013).
33. Sandberg, R., Neilson, J. R., Sarma, A., Sharp, P. A. & Burge, C. B. Proliferating cells express mRNAs with shortened 3? untranslated regions and fewer microRNA target sites. Science 320, 1643-1647 (2008).
34. Ma, F. et al. The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon. Nature Immunol. 12, 861-869 (2011).
35. Smith, K. M. et al. miR-29ab1 deficiency identifies a negative feedback loop controlling Th1 bias that is dysregulated in multiple sclerosis. J. Immunol. 189, 1567-1576 (2012). References 31, 34 and 35 show that miR-29 is an important regulator of IFN production in TH1 cells.
36. Li, Q. J. et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129, 147-161 (2007).
37. Ebert, P. J., Jiang, S., Xie, J., Li, Q. J. & Davis, M. M. An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a. Nature Immunol. 10, 1162-1169 (2009).
38. Henao-Mejia, J. et al. The MicroRNA miR-181 is a critical cellular metabolic rheostat essential for NKT cell ontogenesis and lymphocyte development and homeostasis. Immunity 38, 984-997 (2013).
39. Fragoso, R. et al. Modulating the strength and threshold of NOTCH oncogenic signals by mir-181a-1/b-1. PLoS Genet. 8, e1002855 (2012).
40. Zietara, N. et al. Critical role for miR-181a/b-1 in agonist selection of invariant natural killer T cells. Proc. Natl Acad. Sci. USA 110, 7407-7412 (2013).
41. Li, G. et al. Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity. Nature Med. 18, 1518-1524 (2012).
42. Palin, A. C., Ramachandran, V., Acharya, S. & Lewis, D. B. Human neonatal naive CD4+ T cells have enhanced activation-dependent signaling regulated by the MicroRNA miR-181a. J. Immunol. 190, 2682-2691 (2013).
43. Rusca, N. et al. miR-146a and NF-B1 regulate mast cell survival and T lymphocyte differentiation. Mol. Cell. Biol. 32, 4432-4444 (2012).
44. Curtale, G. et al. An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes. Blood 115, 265-273 (2010).
45. Zhao, J. L. et al. NF-B dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies. Proc. Natl Acad. Sci. USA 108, 9184-9189 (2011).
46. Yang, L. et al. miR-146a controls the resolution of T cell responses in mice. J. Exp. Med. 209, 1655-1670 (2012).
47. Wu, T. et al. Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8+ T-cell differentiation. Proc. Natl Acad. Sci. USA 109, 9965-9970 (2012).
48. Xiao, C. et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nature Immunol. 9, 405-414 (2008).
49. Loeb, G. B. et al. Transcriptome-wide miR-155 binding map reveals widespread noncanonical MicroRNA targeting. Mol. Cell 48, 760-770 (2012).
50. Iliopoulos, D., Jaeger, S. A., Hirsch, H. A., Bulyk, M. L. & Struhl, K. STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol. Cell 39, 493-506 (2010).
51. Huffaker, T. B. et al. Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity. Cell Rep. 2, 1697-1709 (2012).
52. Banerjee, A., Schambach, F., DeJong, C. S., Hammond, S. M. & Reiner, S. L. Micro-RNA-155 inhibits IFN signaling in CD4+ T cells. Eur. J. Immunol. 40, 225-231 (2010).
53. Thai, T. H. et al. Regulation of the germinal center response by microRNA-155. Science 316, 604-608 (2007).
54. Rodriguez, A. et al. Requirement of bic/microRNA-155 for normal immune function. Science 316, 608-611 (2007).
55. O'Connell, R. M. et al. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity 33, 607-619 (2010).
56. Oertli, M. et al. 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 (2011).
57. Liao, W., Lin, J. X. & Leonard, W. J. Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity 38, 13-25 (2013).
58. Thiele, S., Wittmann, J., Jack, H. M. & Pahl, A. miR-9 enhances IL-2 production in activated human CD4+ T cells by repressing Blimp-1. Eur. J. Immunol. 42, 2100-2108 (2012).
59. Seddiki, N. et al. The microRNA-9/B-lymphocyte-induced maturation protein-1/IL-2 axis is differentially regulated in progressive HIV infection. Eur. J. Immunol. 43, 510-520 (2013).
60. Martins, G. A., Cimmino, L., Liao, J., Magnusdottir, E. & Calame, K. Blimp-1 directly represses Il2 and the Il2 activator Fos, attenuating T cell proliferation and survival. J. Exp. Med. 205, 1959-1965 (2008).
61. Stittrich, A. B. et al. The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes. Nature Immunol. 11, 1057-1062 (2010).
62. Lu, L. F. et al. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell 142, 914-929 (2010).
63. Lu, L. F. et al. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity 30, 80-91 (2009).
64. Jiang, S. et al. Molecular dissection of the miR-17-92 cluster's critical dual roles in promoting Th1 responses and preventing inducible Treg differentiation. Blood 118, 5487-5497 (2011).
65. Lazarevic, V. & Glimcher, L. H. T-bet in disease. Nature Immunol. 12, 597-606 (2011).
66. Lu, T. X., Munitz, A. & Rothenberg, M. E. MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J. Immunol. 182, 4994-5002 (2009).
67. Lu, T. X. et al. MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. J. Immunol. 187, 3362-3373 (2011).
68. Jeker, L. T. & Bluestone, J. A. MicroRNA regulation of T-cell differentiation and function. Immunol. Rev. 253, 65-81 (2013).
69. Beaulieu, A. M. et al. MicroRNA function in NK-cell biology. Immunol. Rev. 253, 40-52 (2013).
70. Allen, J. E. & Maizels, R. M. Diversity and dialogue in immunity to helminths. Nature Rev. Immunol. 11, 375-388 (2011).
71. Locksley, R. M. Asthma and allergic inflammation. Cell 140, 777-783 (2010).
72. Paul, W. E. & Zhu, J. How are TH2-type immune responses initiated and amplified? Nature Rev. Immunol. 10, 225-235 (2010).
73. Sawant, D. V., Wu, H., Kaplan, M. H. & Dent, A. L. The Bcl6 target gene microRNA-21 promotes Th2 differentiation by a T cell intrinsic pathway. Mol. Immunol. 54, 435-442 (2013).
74. Guerau-de-Arellano, M. et al. Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity. Brain 134, 3578-3589 (2011).
75. Seumois, G. et al. An integrated nano-scale approach to profile miRNAs in limited clinical samples. Am. J. Clin. Exp. Immunol. 1, 70-89 (2012).
76. Solberg, O. D. et al. Airway epithelial miRNA expression is altered in asthma. Am. J. Respir. Crit. Care Med. 186, 965-974 (2012).
77. Mattes, J., Collison, A., Plank, M., Phipps, S. & Foster, P. S. Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease. Proc. Natl Acad. Sci. USA 106, 18704-18709 (2009).
78. Collison, A. et al. Altered expression of microRNA in the airway wall in chronic asthma: miR-126 as a potential therapeutic target. BMC Pulm. Med. 11, 29 (2011).
79. Collison, A., Mattes, J., Plank, M. & Foster, P. S. Inhibition of house dust mite-induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment. J. Allergy Clin. Immunol. 128, 160-167.e4 (2011).
80. Polikepahad, S. et al. Proinflammatory role for let-7 microRNAs in experimental asthma. J. Biol. Chem. 285, 30139-30149 (2010).
81. Kumar, M. et al. Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation. J. Allergy Clin. Immunol. 128, 1077-1085.e10 (2011).
82. Swaminathan, S. et al. Differential regulation of the Let-7 family of microRNAs in CD4+ T cells alters IL-10 expression. J. Immunol. 188, 6238-6246 (2012).
83. Korn, T., Bettelli, E., Oukka, M. & Kuchroo, V. K. IL-17 and Th17 cells. Annu. Rev. Immunol. 27, 485-517 (2009).
84. Weaver, C. T., Elson, C. O., Fouser, L. A. & Kolls, J. K. The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin. Annu. Rev. Pathol. 8, 477-512 (2013).
85. Thamilarasan, M., Koczan, D., Hecker, M., Paap, B. & Zettl, U. K. MicroRNAs in multiple sclerosis and experimental autoimmune encephalomyelitis. Autoimmun. Rev. 11, 174-179 (2012).
86. Du, C. et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nature Immunol. 10, 1252-1259 (2009).
87. Takahashi, H. et al. TGF and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells. Nature Immunol. 13, 587-595 (2012).
88. Oestreich, K. J., Huang, A. C. & Weinmann, A. S. The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns. J. Exp. Med. 208, 1001-1013 (2011).
89. Nurieva, R. I. et al. Bcl6 mediates the development of T follicular helper cells. Science 325, 1001-1005 (2009).
90. Yu, D. et al. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31, 457-468 (2009).
91. Lazarevic, V. et al. T-bet represses TH17 differentiation by preventing Runx1-mediated activation of the gene encoding ROR?t. Nature Immunol. 12, 96-104 (2011).
92. Murugaiyan, G., Beynon, V., Mittal, A., Joller, N. & Weiner, H. L. Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis. J. Immunol. 187, 2213-2221 (2011).
93. Mycko, M. P. et al. MicroRNA-301a regulation of a T-helper 17 immune response controls autoimmune demyelination. Proc. Natl Acad. Sci. USA 109, e1248-e1257 (2012).
94. Basu, R., Hatton, R. D. & Weaver, C. T. The Th17 family: flexibility follows function. Immunol. Rev. 252, 89-103 (2013).
95. Ansel, K. M., McHeyzer-Williams, L. J., Ngo, V. N., McHeyzer-Williams, M. G. & Cyster, J. G. In vivo-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines. J. Exp. Med. 190, 1123-1134 (1999).
96. Breitfeld, D. et al. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J. Exp. Med. 192, 1545-1552 (2000).
97. Schaerli, P. et al. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J. Exp. Med. 192, 1553-1562 (2000).
98. Crotty, S. Follicular helper CD4 T cells (TFH). Annu. Rev. Immunol. 29, 621-663 (2011).
99. Craft, J. E. Follicular helper T cells in immunity and systemic autoimmunity. Nature Rev. Rheumatol. 8, 337-347 (2012).
100. Johnston, R. J. et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325, 1006-1010 (2009).
101. Choi, Y. S. et al. ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity 34, 932-946 (2011).
102. Baumjohann, D., Okada, T. & Ansel, K. M. Cutting edge: distinct waves of BCL6 expression during T follicular helper cell development. J. Immunol. 187, 2089-2092 (2011).
103. Haynes, N. M. et al. Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation. J. Immunol. 179, 5099-5108 (2007).
104. Deenick, E. K. et al. Follicular helper T cell differentiation requires continuous antigen presentation that is independent of unique B cell signaling. Immunity 33, 241-253 (2010).
105. Baumjohann, D. et al. Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype. Immunity 38, 596-605 (2013).
106. Baumjohann, D. et al. The microRNA cluster miR-17~92 promotes TFH cell differentiation and represses subset-inappropriate gene expression. Nature Immunol. 14, 840-848 (2013).
107. Vinuesa, C. G. et al. A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature 435, 452-458 (2005).
108. Yu, D. et al. Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA. Nature 450, 299-303 (2007).
109. Glasmacher, E. et al. Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression. Nature Immunol. 11, 725-733 (2010).
110. Kang, S. G. et al. MicroRNAs of the miR-17~92 family are critical regulators of TFH differentiation. Nature Immunol. 14, 849-857 (2013).
111. Pepper, M., Pagan, A. J., Igyarto, B. Z., Taylor, J. J. & Jenkins, M. K. Opposing signals from the Bcl6 transcription factor and the interleukin-2 receptor generate T helper 1 central and effector memory cells. Immunity 35, 583-595 (2011).
112. Nakayamada, S. et al. Early Th1 cell differentiation is marked by a Tfh cell-like transition. Immunity 35, 919-931 (2011).
113. Oestreich, K. J., Mohn, S. E. & Weinmann, A. S. Molecular mechanisms that control the expression and activity of Bcl-6 in TH1 cells to regulate flexibility with a TFH-like gene profile. Nature Immunol. 13, 405-411 (2012).
114. Sallusto, F., Geginat, J. & Lanzavecchia, A. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu. Rev. Immunol. 22, 745-763 (2004).
115. Wing, K. & Sakaguchi, S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nature Immunol. 11, 7-13 (2010).
116. Josefowicz, S. Z., Lu, L. F. & Rudensky, A. Y. Regulatory T cells: mechanisms of differentiation and function. Annu. Rev. Immunol. 30, 531-564 (2012).
117. Zhou, X. et al. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J. Exp. Med. 205, 1983-1991 (2008).
118. Liston, A., Lu, L. F., O'Carroll, D., Tarakhovsky, A. & Rudensky, A. Y. Dicer-dependent microRNA pathway safeguards regulatory T cell function. J. Exp. Med. 205, 1993-2004 (2008).
119. Zheng, Y. et al. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 445, 936-940 (2007).
120. Marson, A. et al. Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature 445, 931-935 (2007).
121. de Kouchkovsky, D. et al. miR-17~92 regulates interleukin-10 production by Tregs and control of experimental autoimmune encephalomyelitis. J. Immunol. http://dx.doi.org/10.4049/jimmunol.1203567 (2013).
122. Jeker, L. T. et al. MicroRNA 10a marks regulatory T cells. PLoS ONE 7, e36684 (2012).
123. Tsuji, M. et al. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 323, 1488-1492 (2009).
124. Ansel, K. M. RNA regulation of the immune system. Immunol. Rev. 253, 5-11 (2013).
125. Pagani, M. et al. Role of microRNAs and long-non-coding RNAs in CD4+ T-cell differentiation. Immunol. Rev. 253, 82-96 (2013).
126. Dooley, J., Linterman, M. A. & Liston, A. MicroRNA regulation of T-cell development. Immunol. Rev. 253, 53-64 (2013).
127. Petrocca, F. & Lieberman, J. Promise and challenge of RNA interference-based therapy for cancer. J. Clin. Oncol. 29, 747-754 (2011).
128. Janssen, H. L. et al. Treatment of HCV infection by targeting microRNA. N. Engl. J. Med. 368, 1685-1694 (2013).
129. Peer, D. A daunting task: manipulating leukocyte function with RNAi. Immunol. Rev. 253, 185-197 (2013).
130. Fabian, M. R. & Sonenberg, N. The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nature Struct. Mol. Biol. 19, 586-593 (2012).
131. Leshkowitz, D., Horn-Saban, S., Parmet, Y. & Feldmesser, E. Differences in microRNA detection levels are technology and sequence dependent. RNA 19, 527-538 (2013).
132. Kozomara, A. & Griffiths-Jones, S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 39, D152-D157 (2011).
133. Friedman, R. C., Farh, K. K., Burge, C. B. & Bartel, D. P. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19, 92-105 (2009).
134. Hsu, S. D. et al. miRTarBase: a database curates experimentally validated microRNA-target interactions. Nucleic Acids Res. 39, D163-D169 (2011).
135. Prosser, H. M., Koike-Yusa, H., Cooper, J. D., Law, F. C. & Bradley, A. A resource of vectors and ES cells for targeted deletion of microRNAs in mice. Nature Biotech. 29, 840-845 (2011).
136. Park, C. Y. et al. A resource for the conditional ablation of microRNAs in the mouse. Cell Rep. 1, 385-391 (2012).
137. Brown, B. D. & Naldini, L. Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nature Rev. Genet. 10, 578-585 (2009).
138. Thomas, M., Lieberman, J. & Lal, A. Desperately seeking microRNA targets. Nature Struct. Mol. Biol. 17, 1169-1174 (2010).
139. Chi, S. W., Zang, J. B., Mele, A. & Darnell, R. B. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 460, 479-486 (2009).
140. Hafner, M. et al. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141, 129-141 (2010).