Skip to main content
Top
Published in: Journal of Translational Medicine 1/2014

Open Access 01-12-2014 | Research

A microRNA profile of human CD8+ regulatory T cells and characterization of the effects of microRNAs on Treg cell-associated genes

Authors: Fadi Jebbawi, Hussein Fayyad-Kazan, Makram Merimi, Philippe Lewalle, Jean-Christophe Verougstraete, Oberdan Leo, Pedro Romero, Arsene Burny, Bassam Badran, Philippe Martiat, Redouane Rouas

Published in: Journal of Translational Medicine | Issue 1/2014

Login to get access

Abstract

Background

Recently, regulatory T (Treg) cells have gained interest in the fields of immunopathology, transplantation and oncoimmunology. Here, we investigated the microRNA expression profile of human natural CD8+CD25+ Treg cells and the impact of microRNAs on molecules associated with immune regulation.

Methods

We purified human natural CD8+ Treg cells and assessed the expression of FOXP3 and CTLA-4 by flow cytometry. We have also tested the ex vivo suppressive capacity of these cells in mixed leukocyte reactions. Using TaqMan low-density arrays and microRNA qPCR for validation, we could identify a microRNA ‘signature’ for CD8+CD25+FOXP3+CTLA-4+ natural Treg cells. We used the ‘TargetScan’ and ‘miRBase’ bioinformatics programs to identify potential target sites for these microRNAs in the 3′-UTR of important Treg cell-associated genes.

Results

The human CD8+CD25+ natural Treg cell microRNA signature includes 10 differentially expressed microRNAs. We demonstrated an impact of this signature on Treg cell biology by showing specific regulation of FOXP3, CTLA-4 and GARP gene expression by microRNA using site-directed mutagenesis and a dual-luciferase reporter assay. Furthermore, we used microRNA transduction experiments to demonstrate that these microRNAs impacted their target genes in human primary Treg cells ex vivo.

Conclusions

We are examining the biological relevance of this ‘signature’ by studying its impact on other important Treg cell-associated genes. These efforts could result in a better understanding of the regulation of Treg cell function and might reveal new targets for immunotherapy in immune disorders and cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Dinesh RK, Skaggs BJ, La Cava A, Hahn BH, Singh RP: CD8+ Tregs in lupus, autoimmunity, and beyond. Autoimmun Rev. 2010, 9 (8): 560-568. 10.1016/j.autrev.2010.03.006.PubMedCentralCrossRefPubMed Dinesh RK, Skaggs BJ, La Cava A, Hahn BH, Singh RP: CD8+ Tregs in lupus, autoimmunity, and beyond. Autoimmun Rev. 2010, 9 (8): 560-568. 10.1016/j.autrev.2010.03.006.PubMedCentralCrossRefPubMed
2.
go back to reference Daniele N, Scerpa MC, Landi F, Caniglia M, Miele MJ, Locatelli F, Isacchi G, Zinno F: T(reg) cells: collection, processing, storage and clinical use. Pathol Res Pract. 2011, 207 (4): 209-215. 10.1016/j.prp.2011.02.003.CrossRefPubMed Daniele N, Scerpa MC, Landi F, Caniglia M, Miele MJ, Locatelli F, Isacchi G, Zinno F: T(reg) cells: collection, processing, storage and clinical use. Pathol Res Pract. 2011, 207 (4): 209-215. 10.1016/j.prp.2011.02.003.CrossRefPubMed
3.
go back to reference Huseby ES, Liggitt D, Brabb T, Schnabel B, Ohlen C, Goverman J: A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis. J Exp Med. 2001, 194 (5): 669-676. 10.1084/jem.194.5.669.PubMedCentralCrossRefPubMed Huseby ES, Liggitt D, Brabb T, Schnabel B, Ohlen C, Goverman J: A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis. J Exp Med. 2001, 194 (5): 669-676. 10.1084/jem.194.5.669.PubMedCentralCrossRefPubMed
4.
go back to reference Liblau RS, Wong FS, Mars LT, Santamaria P: Autoreactive CD8 T cells in organ-specific autoimmunity: emerging targets for therapeutic intervention. Immunity. 2002, 17 (1): 1-6. 10.1016/S1074-7613(02)00338-2.CrossRefPubMed Liblau RS, Wong FS, Mars LT, Santamaria P: Autoreactive CD8 T cells in organ-specific autoimmunity: emerging targets for therapeutic intervention. Immunity. 2002, 17 (1): 1-6. 10.1016/S1074-7613(02)00338-2.CrossRefPubMed
5.
go back to reference Miller A, Lider O, Roberts AB, Sporn MB, Weiner HL: Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proc Natl Acad Sci U S A. 1992, 89 (1): 421-425. 10.1073/pnas.89.1.421.PubMedCentralCrossRefPubMed Miller A, Lider O, Roberts AB, Sporn MB, Weiner HL: Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proc Natl Acad Sci U S A. 1992, 89 (1): 421-425. 10.1073/pnas.89.1.421.PubMedCentralCrossRefPubMed
6.
go back to reference Zhang GX, Ma CG, Xiao BG, Bakhiet M, Link H, Olsson T: Depletion of CD8+ T cells suppresses the development of experimental autoimmune myasthenia gravis in Lewis rats. Eur J Immunol. 1995, 25 (5): 1191-1198. 10.1002/eji.1830250509.CrossRefPubMed Zhang GX, Ma CG, Xiao BG, Bakhiet M, Link H, Olsson T: Depletion of CD8+ T cells suppresses the development of experimental autoimmune myasthenia gravis in Lewis rats. Eur J Immunol. 1995, 25 (5): 1191-1198. 10.1002/eji.1830250509.CrossRefPubMed
7.
go back to reference Martin PJ: Donor CD8 cells prevent allogeneic marrow graft rejection in mice: potential implications for marrow transplantation in humans. J Exp Med. 1993, 178 (2): 703-712. 10.1084/jem.178.2.703.CrossRefPubMed Martin PJ: Donor CD8 cells prevent allogeneic marrow graft rejection in mice: potential implications for marrow transplantation in humans. J Exp Med. 1993, 178 (2): 703-712. 10.1084/jem.178.2.703.CrossRefPubMed
8.
go back to reference Fowler DH, Breglio J, Nagel G, Eckhaus MA, Gress RE: Allospecific CD8+ Tc1 and Tc2 populations in graft-versus-leukemia effect and graft-versus-host disease. J Immunol. 1996, 157 (11): 4811-4821.PubMed Fowler DH, Breglio J, Nagel G, Eckhaus MA, Gress RE: Allospecific CD8+ Tc1 and Tc2 populations in graft-versus-leukemia effect and graft-versus-host disease. J Immunol. 1996, 157 (11): 4811-4821.PubMed
9.
go back to reference Prezzi C, Casciaro MA, Francavilla V, Schiaffella E, Finocchi L, Chircu LV, Bruno G, Sette A, Abrignani S, Barnaba V: Virus-specific CD8(+) T cells with type 1 or type 2 cytokine profile are related to different disease activity in chronic hepatitis C virus infection. Eur J Immunol. 2001, 31 (3): 894-906. 10.1002/1521-4141(200103)31:3<894::AID-IMMU894>3.0.CO;2-I.CrossRefPubMed Prezzi C, Casciaro MA, Francavilla V, Schiaffella E, Finocchi L, Chircu LV, Bruno G, Sette A, Abrignani S, Barnaba V: Virus-specific CD8(+) T cells with type 1 or type 2 cytokine profile are related to different disease activity in chronic hepatitis C virus infection. Eur J Immunol. 2001, 31 (3): 894-906. 10.1002/1521-4141(200103)31:3<894::AID-IMMU894>3.0.CO;2-I.CrossRefPubMed
10.
go back to reference Hu D, Weiner HL, Ritz J: Identification of cytolytic Cytolytic CD161−CD56+ Regulatory CD8 T Cells in Human Peripheral Blood. PLoS One. 2013, 8: e59545-10.1371/journal.pone.0059545.PubMedCentralCrossRefPubMed Hu D, Weiner HL, Ritz J: Identification of cytolytic Cytolytic CD161CD56+ Regulatory CD8 T Cells in Human Peripheral Blood. PLoS One. 2013, 8: e59545-10.1371/journal.pone.0059545.PubMedCentralCrossRefPubMed
11.
go back to reference Xystrakis E, Dejean AS, Bernard I, Druet P, Liblau R, Gonzalez-Dunia D, Saoudi A: Identification of a novel natural regulatory CD8 T-cell subset and analysis of its mechanism of regulation. Blood. 2004, 104 (10): 3294-3301. 10.1182/blood-2004-03-1214.CrossRefPubMed Xystrakis E, Dejean AS, Bernard I, Druet P, Liblau R, Gonzalez-Dunia D, Saoudi A: Identification of a novel natural regulatory CD8 T-cell subset and analysis of its mechanism of regulation. Blood. 2004, 104 (10): 3294-3301. 10.1182/blood-2004-03-1214.CrossRefPubMed
12.
go back to reference Uss E, Rowshani AT, Hooibrink B, Lardy NM, van Lier RA, ten Berge IJ: CD103 is a marker for alloantigen-induced regulatory CD8+ T cells. J Immunol. 2006, 177 (5): 2775-2783. 10.4049/jimmunol.177.5.2775.CrossRefPubMed Uss E, Rowshani AT, Hooibrink B, Lardy NM, van Lier RA, ten Berge IJ: CD103 is a marker for alloantigen-induced regulatory CD8+ T cells. J Immunol. 2006, 177 (5): 2775-2783. 10.4049/jimmunol.177.5.2775.CrossRefPubMed
13.
go back to reference Tilburgs T, Roelen DL, van der Mast BJ, van Schip JJ, Kleijburg C, Groot-Swings GM, Kanhai HH, Claas FH, Scherjon SA: Differential distribution of CD4(+)CD25(bright) and CD8(+)CD28(−) T-cells in decidua and maternal blood during human pregnancy. Placenta. 2006, 27 (Suppl A): S47-S53. 10.1016/j.placenta.2005.11.008.CrossRefPubMed Tilburgs T, Roelen DL, van der Mast BJ, van Schip JJ, Kleijburg C, Groot-Swings GM, Kanhai HH, Claas FH, Scherjon SA: Differential distribution of CD4(+)CD25(bright) and CD8(+)CD28(−) T-cells in decidua and maternal blood during human pregnancy. Placenta. 2006, 27 (Suppl A): S47-S53. 10.1016/j.placenta.2005.11.008.CrossRefPubMed
14.
go back to reference Tennakoon DK, Mehta RS, Ortega SB, Bhoj V, Racke MK, Karandikar NJ: Therapeutic induction of regulatory, cytotoxic CD8+ T cells in multiple sclerosis. J Immunol. 2006, 176 (11): 7119-7129. 10.4049/jimmunol.176.11.7119.CrossRefPubMed Tennakoon DK, Mehta RS, Ortega SB, Bhoj V, Racke MK, Karandikar NJ: Therapeutic induction of regulatory, cytotoxic CD8+ T cells in multiple sclerosis. J Immunol. 2006, 176 (11): 7119-7129. 10.4049/jimmunol.176.11.7119.CrossRefPubMed
15.
go back to reference Shao L, Jacobs AR, Johnson VV, Mayer L: Activation of CD8+ regulatory T cells by human placental trophoblasts. J Immunol. 2005, 174 (12): 7539-7547. 10.4049/jimmunol.174.12.7539.CrossRefPubMed Shao L, Jacobs AR, Johnson VV, Mayer L: Activation of CD8+ regulatory T cells by human placental trophoblasts. J Immunol. 2005, 174 (12): 7539-7547. 10.4049/jimmunol.174.12.7539.CrossRefPubMed
16.
go back to reference Popescu I, Macedo C, Abu-Elmagd K, Shapiro R, Hua Y, Thomson AW, Morelli AE, Storkus WJ, Metes D: EBV-specific CD8+ T cell reactivation in transplant patients results in expansion of CD8+ type-1 regulatory T cells. Am J Transplant. 2007, 7 (5): 1215-1223. 10.1111/j.1600-6143.2007.01740.x.CrossRefPubMed Popescu I, Macedo C, Abu-Elmagd K, Shapiro R, Hua Y, Thomson AW, Morelli AE, Storkus WJ, Metes D: EBV-specific CD8+ T cell reactivation in transplant patients results in expansion of CD8+ type-1 regulatory T cells. Am J Transplant. 2007, 7 (5): 1215-1223. 10.1111/j.1600-6143.2007.01740.x.CrossRefPubMed
17.
go back to reference Joosten SA, van Meijgaarden KE, Savage ND, de Boer T, Triebel F, van der Wal A, de Heer E, Klein MR, Geluk A, Ottenhoff TH: Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4. Proc Natl Acad Sci U S A. 2007, 104 (19): 8029-8034. 10.1073/pnas.0702257104.PubMedCentralCrossRefPubMed Joosten SA, van Meijgaarden KE, Savage ND, de Boer T, Triebel F, van der Wal A, de Heer E, Klein MR, Geluk A, Ottenhoff TH: Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4. Proc Natl Acad Sci U S A. 2007, 104 (19): 8029-8034. 10.1073/pnas.0702257104.PubMedCentralCrossRefPubMed
18.
go back to reference Filaci G, Fenoglio D, Fravega M, Ansaldo G, Borgonovo G, Traverso P, Villaggio B, Ferrera A, Kunkl A, Rizzi M, Ferrera F, Balestra P, Ghio M, Contini P, Setti M, Olive D, Azzarone B, Carmignani G, Ravetti JL, Torre G, Indiveri F: CD8+ CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers. J Immunol. 2007, 179 (7): 4323-4334. 10.4049/jimmunol.179.7.4323.CrossRefPubMed Filaci G, Fenoglio D, Fravega M, Ansaldo G, Borgonovo G, Traverso P, Villaggio B, Ferrera A, Kunkl A, Rizzi M, Ferrera F, Balestra P, Ghio M, Contini P, Setti M, Olive D, Azzarone B, Carmignani G, Ravetti JL, Torre G, Indiveri F: CD8+ CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers. J Immunol. 2007, 179 (7): 4323-4334. 10.4049/jimmunol.179.7.4323.CrossRefPubMed
19.
go back to reference Cosmi L, Liotta F, Lazzeri E, Francalanci M, Angeli R, Mazzinghi B, Santarlasci V, Manetti R, Vanini V, Romagnani P, Maggi E, Romagnani S, Annunziato F: Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood. 2003, 102 (12): 4107-4114. 10.1182/blood-2003-04-1320.CrossRefPubMed Cosmi L, Liotta F, Lazzeri E, Francalanci M, Angeli R, Mazzinghi B, Santarlasci V, Manetti R, Vanini V, Romagnani P, Maggi E, Romagnani S, Annunziato F: Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood. 2003, 102 (12): 4107-4114. 10.1182/blood-2003-04-1320.CrossRefPubMed
20.
go back to reference Colovai AI, Mirza M, Vlad G, Wang S, Ho E, Cortesini R, Suciu-Foca N: Regulatory CD8+CD28- T cells in heart transplant recipients. Hum Immunol. 2003, 64 (1): 31-37. 10.1016/S0198-8859(02)00742-5.CrossRefPubMed Colovai AI, Mirza M, Vlad G, Wang S, Ho E, Cortesini R, Suciu-Foca N: Regulatory CD8+CD28- T cells in heart transplant recipients. Hum Immunol. 2003, 64 (1): 31-37. 10.1016/S0198-8859(02)00742-5.CrossRefPubMed
21.
go back to reference Chang CC, Ciubotariu R, Manavalan JS, Yuan J, Colovai AI, Piazza F, Lederman S, Colonna M, Cortesini R, Dalla-Favera R, Suciu-Foca N: Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol. 2002, 3 (3): 237-243. 10.1038/ni760.CrossRefPubMed Chang CC, Ciubotariu R, Manavalan JS, Yuan J, Colovai AI, Piazza F, Lederman S, Colonna M, Cortesini R, Dalla-Favera R, Suciu-Foca N: Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol. 2002, 3 (3): 237-243. 10.1038/ni760.CrossRefPubMed
22.
go back to reference Cai J, Lee J, Jankowska-Gan E, Derks R, Pool J, Mutis T, Goulmy E, Burlingham WJ: Minor H antigen HA-1-specific regulator and effector CD8+ T cells, and HA-1 microchimerism, in allograft tolerance. J Exp Med. 2004, 199 (7): 1017-1023. 10.1084/jem.20031012.PubMedCentralCrossRefPubMed Cai J, Lee J, Jankowska-Gan E, Derks R, Pool J, Mutis T, Goulmy E, Burlingham WJ: Minor H antigen HA-1-specific regulator and effector CD8+ T cells, and HA-1 microchimerism, in allograft tolerance. J Exp Med. 2004, 199 (7): 1017-1023. 10.1084/jem.20031012.PubMedCentralCrossRefPubMed
23.
go back to reference Brimnes J, Allez M, Dotan I, Shao L, Nakazawa A, Mayer L: Defects in CD8+ regulatory T cells in the lamina propria of patients with inflammatory bowel disease. J Immunol. 2005, 174 (9): 5814-5822. 10.4049/jimmunol.174.9.5814.CrossRefPubMed Brimnes J, Allez M, Dotan I, Shao L, Nakazawa A, Mayer L: Defects in CD8+ regulatory T cells in the lamina propria of patients with inflammatory bowel disease. J Immunol. 2005, 174 (9): 5814-5822. 10.4049/jimmunol.174.9.5814.CrossRefPubMed
24.
go back to reference Bisikirska B, Colgan J, Luban J, Bluestone JA, Herold KC: TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs. J Clin Invest. 2005, 115 (10): 2904-2913. 10.1172/JCI23961.PubMedCentralCrossRefPubMed Bisikirska B, Colgan J, Luban J, Bluestone JA, Herold KC: TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs. J Clin Invest. 2005, 115 (10): 2904-2913. 10.1172/JCI23961.PubMedCentralCrossRefPubMed
25.
go back to reference Billerbeck E, Blum HE, Thimme R: Parallel expansion of human virus-specific FoxP3- effector memory and de novo-generated FoxP3+ regulatory CD8 T cells upon antigen recognition in vitro. J Immunol. 2007, 179 (2): 1039-1048. 10.4049/jimmunol.179.2.1039.CrossRefPubMed Billerbeck E, Blum HE, Thimme R: Parallel expansion of human virus-specific FoxP3- effector memory and de novo-generated FoxP3+ regulatory CD8 T cells upon antigen recognition in vitro. J Immunol. 2007, 179 (2): 1039-1048. 10.4049/jimmunol.179.2.1039.CrossRefPubMed
26.
go back to reference Gilliet M, Liu YJ: Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J Exp Med. 2002, 195 (6): 695-704. 10.1084/jem.20011603.PubMedCentralCrossRefPubMed Gilliet M, Liu YJ: Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J Exp Med. 2002, 195 (6): 695-704. 10.1084/jem.20011603.PubMedCentralCrossRefPubMed
27.
go back to reference Shi Z, Okuno Y, Rifa'i M, Endharti AT, Akane K, Isobe K, Suzuki H: Human CD8+CXCR3+ T cells have the same function as murine CD8+CD122+ Treg. Eur J Immunol. 2009, 39: 2106-2119. 10.1002/eji.200939314.CrossRefPubMed Shi Z, Okuno Y, Rifa'i M, Endharti AT, Akane K, Isobe K, Suzuki H: Human CD8+CXCR3+ T cells have the same function as murine CD8+CD122+ Treg. Eur J Immunol. 2009, 39: 2106-2119. 10.1002/eji.200939314.CrossRefPubMed
28.
go back to reference Yagi H, Nomura T, Nakamura K, Yamazaki S, Kitawaki T, Hori S, Maeda M, Onodera M, Uchiyama T, Fujii S, Sakaguchi S: Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int Immunol. 2004, 16 (11): 1643-1656. 10.1093/intimm/dxh165.CrossRefPubMed Yagi H, Nomura T, Nakamura K, Yamazaki S, Kitawaki T, Hori S, Maeda M, Onodera M, Uchiyama T, Fujii S, Sakaguchi S: Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int Immunol. 2004, 16 (11): 1643-1656. 10.1093/intimm/dxh165.CrossRefPubMed
29.
go back to reference Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL, Buist N, Levy-Lahad E, Mazzella M, Goulet O, Perroni L, Bricarelli FD, Byrne G, McEuen M, Proll S, Appleby M, Brunkow ME: X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001, 27 (1): 18-20. 10.1038/83707.CrossRefPubMed Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL, Buist N, Levy-Lahad E, Mazzella M, Goulet O, Perroni L, Bricarelli FD, Byrne G, McEuen M, Proll S, Appleby M, Brunkow ME: X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001, 27 (1): 18-20. 10.1038/83707.CrossRefPubMed
30.
go back to reference Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD: The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001, 27 (1): 20-21. 10.1038/83713.CrossRefPubMed Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD: The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001, 27 (1): 20-21. 10.1038/83713.CrossRefPubMed
31.
go back to reference Khattri R, Cox T, Yasayko SA, Ramsdell F: An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol. 2003, 4 (4): 337-342. 10.1038/ni909.CrossRefPubMed Khattri R, Cox T, Yasayko SA, Ramsdell F: An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol. 2003, 4 (4): 337-342. 10.1038/ni909.CrossRefPubMed
32.
go back to reference Buckner JH, Ziegler SF: Functional analysis of FOXP3. Ann NY Acad Sci. 2008, 1143: 151-169. 10.1196/annals.1443.014.CrossRefPubMed Buckner JH, Ziegler SF: Functional analysis of FOXP3. Ann NY Acad Sci. 2008, 1143: 151-169. 10.1196/annals.1443.014.CrossRefPubMed
33.
go back to reference Kolar P, Knieke K, Hegel JK, Quandt D, Burmester GR, Hoff H, Brunner-Weinzierl MC: CTLA-4 (CD152) controls homeostasis and suppressive capacity of regulatory T cells in mice. Arthritis Rheum. 2009, 60 (1): 123-132. 10.1002/art.24181.CrossRefPubMed Kolar P, Knieke K, Hegel JK, Quandt D, Burmester GR, Hoff H, Brunner-Weinzierl MC: CTLA-4 (CD152) controls homeostasis and suppressive capacity of regulatory T cells in mice. Arthritis Rheum. 2009, 60 (1): 123-132. 10.1002/art.24181.CrossRefPubMed
34.
go back to reference Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003, 299 (5609): 1057-1061. 10.1126/science.1079490.CrossRefPubMed Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003, 299 (5609): 1057-1061. 10.1126/science.1079490.CrossRefPubMed
35.
go back to reference Fontenot JD, Gavin MA, Rudensky AY: Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003, 4 (4): 330-336. 10.1038/ni904.CrossRefPubMed Fontenot JD, Gavin MA, Rudensky AY: Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003, 4 (4): 330-336. 10.1038/ni904.CrossRefPubMed
36.
go back to reference Wang R, Kozhaya L, Mercer F, Khaitan A, Fujii H, Unutmaz D: Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells. Proc Natl Acad Sci U S A. 2009, 106: 13439-13444. 10.1073/pnas.0901965106.PubMedCentralCrossRefPubMed Wang R, Kozhaya L, Mercer F, Khaitan A, Fujii H, Unutmaz D: Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells. Proc Natl Acad Sci U S A. 2009, 106: 13439-13444. 10.1073/pnas.0901965106.PubMedCentralCrossRefPubMed
37.
go back to reference Ariyan C, Salvalaggio P, Fecteau S, Deng S, Rogozinski L, Mandelbrot D, Sharpe A, Sayegh MH, Basadonna GP, Rothstein DM: Cutting edge: transplantation tolerance through enhanced CTLA-4 expression. J Immunol. 2003, 171 (11): 5673-5677. 10.4049/jimmunol.171.11.5673.CrossRefPubMed Ariyan C, Salvalaggio P, Fecteau S, Deng S, Rogozinski L, Mandelbrot D, Sharpe A, Sayegh MH, Basadonna GP, Rothstein DM: Cutting edge: transplantation tolerance through enhanced CTLA-4 expression. J Immunol. 2003, 171 (11): 5673-5677. 10.4049/jimmunol.171.11.5673.CrossRefPubMed
38.
go back to reference Kavvoura FK, Ioannidis JP: CTLA-4 gene polymorphisms and susceptibility to type 1 diabetes mellitus: a HuGE Review and meta-analysis. Am J Epidemiol. 2005, 162 (1): 3-16. 10.1093/aje/kwi165.CrossRefPubMed Kavvoura FK, Ioannidis JP: CTLA-4 gene polymorphisms and susceptibility to type 1 diabetes mellitus: a HuGE Review and meta-analysis. Am J Epidemiol. 2005, 162 (1): 3-16. 10.1093/aje/kwi165.CrossRefPubMed
39.
go back to reference Ribas A, Camacho LH, Lopez-Berestein G, Pavlov D, Bulanhagui CA, Millham R, Comin-Anduix B, Reuben JM, Seja E, Parker CA, Sharma A, Glaspy JA, Gomez-Navarro J: Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol. 2005, 23 (35): 8968-8977. 10.1200/JCO.2005.01.109.CrossRefPubMed Ribas A, Camacho LH, Lopez-Berestein G, Pavlov D, Bulanhagui CA, Millham R, Comin-Anduix B, Reuben JM, Seja E, Parker CA, Sharma A, Glaspy JA, Gomez-Navarro J: Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol. 2005, 23 (35): 8968-8977. 10.1200/JCO.2005.01.109.CrossRefPubMed
40.
go back to reference Tran DQ, Andersson J, Wang R, Ramsey H, Unutmaz D, Shevach EM: GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells. Proc Natl Acad Sci U S A. 2009, 106: 13445-13450. 10.1073/pnas.0901944106.PubMedCentralCrossRefPubMed Tran DQ, Andersson J, Wang R, Ramsey H, Unutmaz D, Shevach EM: GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells. Proc Natl Acad Sci U S A. 2009, 106: 13445-13450. 10.1073/pnas.0901944106.PubMedCentralCrossRefPubMed
41.
go back to reference Stockis J, Colau D, Coulie PG, Lucas S: Membrane protein GARP is a receptor for latent TGF-beta on the surface of activated human Treg. Eur J Immunol. 2009, 39: 3315-3322. 10.1002/eji.200939684.CrossRefPubMed Stockis J, Colau D, Coulie PG, Lucas S: Membrane protein GARP is a receptor for latent TGF-beta on the surface of activated human Treg. Eur J Immunol. 2009, 39: 3315-3322. 10.1002/eji.200939684.CrossRefPubMed
42.
go back to reference Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN: Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006, 125 (5): 887-901. 10.1016/j.cell.2006.03.043.CrossRefPubMed Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN: Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006, 125 (5): 887-901. 10.1016/j.cell.2006.03.043.CrossRefPubMed
43.
go back to reference Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN: The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003, 425 (6956): 415-419. 10.1038/nature01957.CrossRefPubMed Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN: The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003, 425 (6956): 415-419. 10.1038/nature01957.CrossRefPubMed
44.
go back to reference Lee Y, Han J, Yeom KH, Jin H, Kim VN: Drosha in primary microRNA processing. Cold Spring Harb Symp Quant Biol. 2006, 71: 51-57. 10.1101/sqb.2006.71.041.CrossRefPubMed Lee Y, Han J, Yeom KH, Jin H, Kim VN: Drosha in primary microRNA processing. Cold Spring Harb Symp Quant Biol. 2006, 71: 51-57. 10.1101/sqb.2006.71.041.CrossRefPubMed
45.
go back to reference Yeom KH, Lee Y, Han J, Suh MR, Kim VN: Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing. Nucleic Acids Res. 2006, 34 (16): 4622-4629. 10.1093/nar/gkl458.PubMedCentralCrossRefPubMed Yeom KH, Lee Y, Han J, Suh MR, Kim VN: Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing. Nucleic Acids Res. 2006, 34 (16): 4622-4629. 10.1093/nar/gkl458.PubMedCentralCrossRefPubMed
46.
go back to reference Bohnsack MT, Czaplinski K, Gorlich D: Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA. 2004, 10 (2): 185-191. 10.1261/rna.5167604.PubMedCentralCrossRefPubMed Bohnsack MT, Czaplinski K, Gorlich D: Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA. 2004, 10 (2): 185-191. 10.1261/rna.5167604.PubMedCentralCrossRefPubMed
47.
go back to reference Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, Shiekhattar R: TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005, 436 (7051): 740-744. 10.1038/nature03868.PubMedCentralCrossRefPubMed Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, Shiekhattar R: TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005, 436 (7051): 740-744. 10.1038/nature03868.PubMedCentralCrossRefPubMed
48.
go back to reference Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U: Nuclear export of microRNA precursors. Science. 2004, 303 (5654): 95-98. 10.1126/science.1090599.CrossRefPubMed Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U: Nuclear export of microRNA precursors. Science. 2004, 303 (5654): 95-98. 10.1126/science.1090599.CrossRefPubMed
49.
go back to reference Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, Hannon GJ: Argonaute2 is the catalytic engine of mammalian RNAi. Science. 2004, 305 (5689): 1437-1441. 10.1126/science.1102513.CrossRefPubMed Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, Hannon GJ: Argonaute2 is the catalytic engine of mammalian RNAi. Science. 2004, 305 (5689): 1437-1441. 10.1126/science.1102513.CrossRefPubMed
50.
go back to reference Lingel A, Simon B, Izaurralde E, Sattler M: Structure and nucleic-acid binding of the Drosophila Argonaute 2 PAZ domain. Nature. 2003, 426 (6965): 465-469. 10.1038/nature02123.CrossRefPubMed Lingel A, Simon B, Izaurralde E, Sattler M: Structure and nucleic-acid binding of the Drosophila Argonaute 2 PAZ domain. Nature. 2003, 426 (6965): 465-469. 10.1038/nature02123.CrossRefPubMed
51.
go back to reference Stefani G, Slack FJ: Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol. 2008, 9 (3): 219-230. 10.1038/nrm2347.CrossRefPubMed Stefani G, Slack FJ: Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol. 2008, 9 (3): 219-230. 10.1038/nrm2347.CrossRefPubMed
52.
go back to reference Williams AE: Functional aspects of animal microRNAs. Cell Mol Life Sci. 2008, 65 (4): 545-562. 10.1007/s00018-007-7355-9.CrossRefPubMed Williams AE: Functional aspects of animal microRNAs. Cell Mol Life Sci. 2008, 65 (4): 545-562. 10.1007/s00018-007-7355-9.CrossRefPubMed
53.
go back to reference Tili E, Michaille JJ, Gandhi V, Plunkett W, Sampath D, Calin GA: miRNAs and their potential for use against cancer and other diseases. Future Oncol. 2007, 3 (5): 521-537. 10.2217/14796694.3.5.521.CrossRefPubMed Tili E, Michaille JJ, Gandhi V, Plunkett W, Sampath D, Calin GA: miRNAs and their potential for use against cancer and other diseases. Future Oncol. 2007, 3 (5): 521-537. 10.2217/14796694.3.5.521.CrossRefPubMed
54.
go back to reference Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, Tanaka K, Loeb GB, Lee H, Yoshimura A, Rajewsky K, Rudensky AY: Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity. 2009, 30: 80-91. 10.1016/j.immuni.2008.11.010.PubMedCentralCrossRefPubMed Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, Tanaka K, Loeb GB, Lee H, Yoshimura A, Rajewsky K, Rudensky AY: Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity. 2009, 30: 80-91. 10.1016/j.immuni.2008.11.010.PubMedCentralCrossRefPubMed
55.
go back to reference Zhou Q, Haupt S, Prots I, Thummler K, Kremmer E, Lipsky PE, Schulze-Koops H, Skapenko A: miR-142-3p is involved in CD25+ CD4 T cell proliferation by targeting the expression of glycoprotein A repetitions predominant. J Immunol. 2013, 190: 6579-6588. 10.4049/jimmunol.1202993.CrossRefPubMed Zhou Q, Haupt S, Prots I, Thummler K, Kremmer E, Lipsky PE, Schulze-Koops H, Skapenko A: miR-142-3p is involved in CD25+ CD4 T cell proliferation by targeting the expression of glycoprotein A repetitions predominant. J Immunol. 2013, 190: 6579-6588. 10.4049/jimmunol.1202993.CrossRefPubMed
56.
go back to reference Huang B, Zhao J, Lei Z, Shen S, Li D, Shen GX, Zhang GM, Feng ZH: miR-142-3p restricts cAMP production in CD4+ CD25- T cells and CD4+CD25+ TREG cells by targeting AC9 mRNA. EMBO Rep. 2009, 10: 180-185. 10.1038/embor.2008.224.PubMedCentralCrossRefPubMed Huang B, Zhao J, Lei Z, Shen S, Li D, Shen GX, Zhang GM, Feng ZH: miR-142-3p restricts cAMP production in CD4+ CD25- T cells and CD4+CD25+ TREG cells by targeting AC9 mRNA. EMBO Rep. 2009, 10: 180-185. 10.1038/embor.2008.224.PubMedCentralCrossRefPubMed
57.
go back to reference de Kouchkovsky D, Esensten JH, Rosenthal WL, Morar MM, Bluestone JA, Jeker LT: microRNA-17-92 regulates IL-10 production by Tregs and control of experimental autoimmune encephalomyelitis. J Immunol. 2013, 191: 1594-1605. 10.4049/jimmunol.1203567.PubMedCentralCrossRefPubMed de Kouchkovsky D, Esensten JH, Rosenthal WL, Morar MM, Bluestone JA, Jeker LT: microRNA-17-92 regulates IL-10 production by Tregs and control of experimental autoimmune encephalomyelitis. J Immunol. 2013, 191: 1594-1605. 10.4049/jimmunol.1203567.PubMedCentralCrossRefPubMed
58.
go back to reference Ha TY: The Role of MicroRNAs in Regulatory T Cells and in the Immune Response. Immun Netw. 2011, 11 (1): 11-41. 10.4110/in.2011.11.1.11.CrossRef Ha TY: The Role of MicroRNAs in Regulatory T Cells and in the Immune Response. Immun Netw. 2011, 11 (1): 11-41. 10.4110/in.2011.11.1.11.CrossRef
59.
go back to reference Bresatz S, Sadlon T, Millard D, Zola H, Barry SC: Isolation, propagation and characterization of cord blood derived CD4+ CD25+ regulatory T cells. J Immunol Methods. 2007, 327 (1–2): 53-62. 10.1016/j.jim.2007.06.006.CrossRefPubMed Bresatz S, Sadlon T, Millard D, Zola H, Barry SC: Isolation, propagation and characterization of cord blood derived CD4+ CD25+ regulatory T cells. J Immunol Methods. 2007, 327 (1–2): 53-62. 10.1016/j.jim.2007.06.006.CrossRefPubMed
60.
go back to reference Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D: In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996, 272: 263-267. 10.1126/science.272.5259.263.CrossRefPubMed Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D: In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996, 272: 263-267. 10.1126/science.272.5259.263.CrossRefPubMed
61.
go back to reference Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D: Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol. 1997, 15: 871-875. 10.1038/nbt0997-871.CrossRefPubMed Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D: Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol. 1997, 15: 871-875. 10.1038/nbt0997-871.CrossRefPubMed
62.
go back to reference Yeung ML, Bennasser Y, Le SY, Jeang KT: siRNA, miRNA and HIV: promises and challenges. Cell Res. 2005, 15: 935-946. 10.1038/sj.cr.7290371.CrossRefPubMed Yeung ML, Bennasser Y, Le SY, Jeang KT: siRNA, miRNA and HIV: promises and challenges. Cell Res. 2005, 15: 935-946. 10.1038/sj.cr.7290371.CrossRefPubMed
63.
go back to reference Johnston JC, Gasmi M, Lim LE, Elder JH, Yee JK, Jolly DJ, Campbell KP, Davidson BL, Sauter SL: Minimum requirements for efficient transduction of dividing and nondividing cells by feline immunodeficiency virus vectors. J Virol. 1999, 73: 4991-5000.PubMedCentralPubMed Johnston JC, Gasmi M, Lim LE, Elder JH, Yee JK, Jolly DJ, Campbell KP, Davidson BL, Sauter SL: Minimum requirements for efficient transduction of dividing and nondividing cells by feline immunodeficiency virus vectors. J Virol. 1999, 73: 4991-5000.PubMedCentralPubMed
64.
go back to reference Abbas-Terki T, Blanco-Bose W, Deglon N, Pralong W, Aebischer P: Lentiviral-mediated RNA interference. Hum Gene Ther. 2002, 13: 2197-2201. 10.1089/104303402320987888.CrossRefPubMed Abbas-Terki T, Blanco-Bose W, Deglon N, Pralong W, Aebischer P: Lentiviral-mediated RNA interference. Hum Gene Ther. 2002, 13: 2197-2201. 10.1089/104303402320987888.CrossRefPubMed
65.
go back to reference Cobb BS, Hertweck A, Smith J, O'Connor E, Graf D, Cook T, Smale ST, Sakaguchi S, Livesey FJ, Fisher AG, Merkenschlager M: A role for Dicer in immune regulation. J Exp Med. 2006, 203: 2519-2527. 10.1084/jem.20061692.PubMedCentralCrossRefPubMed Cobb BS, Hertweck A, Smith J, O'Connor E, Graf D, Cook T, Smale ST, Sakaguchi S, Livesey FJ, Fisher AG, Merkenschlager M: A role for Dicer in immune regulation. J Exp Med. 2006, 203: 2519-2527. 10.1084/jem.20061692.PubMedCentralCrossRefPubMed
66.
go back to reference Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade II, Gunsalus KC, Stoffel M, Rajewsky N: Combinatorial microRNA target predictions. Nat Genet. 2005, 37 (5): 495-500. 10.1038/ng1536.CrossRefPubMed Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade II, Gunsalus KC, Stoffel M, Rajewsky N: Combinatorial microRNA target predictions. Nat Genet. 2005, 37 (5): 495-500. 10.1038/ng1536.CrossRefPubMed
67.
go back to reference Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP: MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell. 2007, 27 (1): 91-105. 10.1016/j.molcel.2007.06.017.PubMedCentralCrossRefPubMed Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP: MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell. 2007, 27 (1): 91-105. 10.1016/j.molcel.2007.06.017.PubMedCentralCrossRefPubMed
68.
go back to reference Rouas R, Fayyad-Kazan H, El Zein N, Lewalle P, Rothe F, Simion A, Akl H, Mourtada M, El Rifai M, Burny A, Romero P, Martiat P, Badran B: Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression. Eur J Immunol. 2009, 39 (6): 1608-1618. 10.1002/eji.200838509.CrossRefPubMed Rouas R, Fayyad-Kazan H, El Zein N, Lewalle P, Rothe F, Simion A, Akl H, Mourtada M, El Rifai M, Burny A, Romero P, Martiat P, Badran B: Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression. Eur J Immunol. 2009, 39 (6): 1608-1618. 10.1002/eji.200838509.CrossRefPubMed
69.
go back to reference Fayyad-Kazan H, Rouas R, Fayyad-Kazan M, Badran R, El Zein N, Lewalle P, Najar M, Hamade E, Jebbawi F, Merimi M, Romero P, Burny A, Badran B, Martiat P: MicroRNA profile of circulating CD4+ regulatory T cells in human adults and impact of differentially expressed microRNAs on expression of two genes essential to their function. J Biol Chem. 2012, 287 (13): 9910-9922. 10.1074/jbc.M111.337154.PubMedCentralCrossRefPubMed Fayyad-Kazan H, Rouas R, Fayyad-Kazan M, Badran R, El Zein N, Lewalle P, Najar M, Hamade E, Jebbawi F, Merimi M, Romero P, Burny A, Badran B, Martiat P: MicroRNA profile of circulating CD4+ regulatory T cells in human adults and impact of differentially expressed microRNAs on expression of two genes essential to their function. J Biol Chem. 2012, 287 (13): 9910-9922. 10.1074/jbc.M111.337154.PubMedCentralCrossRefPubMed
70.
go back to reference Pandiyan P, Gartner D, Soezeri O, Radbruch A, Schulze-Osthoff K, Brunner-Weinzierl MC: CD152 (CTLA-4) determines the unequal resistance of Th1 and Th2 cells against activation-induced cell death by a mechanism requiring PI3 kinase function. J Exp Med. 2004, 199 (6): 831-842. 10.1084/jem.20031058.PubMedCentralCrossRefPubMed Pandiyan P, Gartner D, Soezeri O, Radbruch A, Schulze-Osthoff K, Brunner-Weinzierl MC: CD152 (CTLA-4) determines the unequal resistance of Th1 and Th2 cells against activation-induced cell death by a mechanism requiring PI3 kinase function. J Exp Med. 2004, 199 (6): 831-842. 10.1084/jem.20031058.PubMedCentralCrossRefPubMed
71.
go back to reference Gauthy E, Cuende J, Stockis J, Huygens C, Lethe B, Collet JF, Bommer G, Coulie PG, Lucas S: GARP Is Regulated by miRNAs and Controls Latent TGF-beta1 Production by Human Regulatory T Cells. PLoS One. 2013, 8: e76186-10.1371/journal.pone.0076186.PubMedCentralCrossRefPubMed Gauthy E, Cuende J, Stockis J, Huygens C, Lethe B, Collet JF, Bommer G, Coulie PG, Lucas S: GARP Is Regulated by miRNAs and Controls Latent TGF-beta1 Production by Human Regulatory T Cells. PLoS One. 2013, 8: e76186-10.1371/journal.pone.0076186.PubMedCentralCrossRefPubMed
72.
go back to reference Dudda JC, Salaun B, Ji Y, Palmer DC, Monnot GC, Merck E, Boudousquie C, Utzschneider DT, Escobar TM, Perret R, Muljo SA, Hebeisen M, Rufer N, Zehn D, Donda A, Restifo NP, Held W, Gattinoni L, Romero P: MicroRNA-155 is required for effector CD8+ T cell responses to virus infection and cancer. Immunity. 2013, 38: 742-753. 10.1016/j.immuni.2012.12.006.PubMedCentralCrossRefPubMed Dudda JC, Salaun B, Ji Y, Palmer DC, Monnot GC, Merck E, Boudousquie C, Utzschneider DT, Escobar TM, Perret R, Muljo SA, Hebeisen M, Rufer N, Zehn D, Donda A, Restifo NP, Held W, Gattinoni L, Romero P: MicroRNA-155 is required for effector CD8+ T cell responses to virus infection and cancer. Immunity. 2013, 38: 742-753. 10.1016/j.immuni.2012.12.006.PubMedCentralCrossRefPubMed
Metadata
Title
A microRNA profile of human CD8+ regulatory T cells and characterization of the effects of microRNAs on Treg cell-associated genes
Authors
Fadi Jebbawi
Hussein Fayyad-Kazan
Makram Merimi
Philippe Lewalle
Jean-Christophe Verougstraete
Oberdan Leo
Pedro Romero
Arsene Burny
Bassam Badran
Philippe Martiat
Redouane Rouas
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2014
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-014-0218-x

Other articles of this Issue 1/2014

Journal of Translational Medicine 1/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.