title: Distinct translational control in CD4+ T cell subsets.
abstract: Regulatory T cells expressing the transcription factor Foxp3 play indispensable roles for the induction and maintenance of immunological self-tolerance and immune homeostasis. Genome-wide mRNA expression studies have defined canonical signatures of T cell subsets. Changes in steady-state mRNA levels, however, often do not reflect those of corresponding proteins due to post-transcriptional mechanisms including mRNA translation. Here, we unveil a unique translational signature, contrasting CD4(+)Foxp3(+) regulatory T (T(Foxp3+)) and CD4(+)Foxp3(-) non-regulatory T (TFoxp3-) cells, which imprints subset-specific protein expression. We further show that translation of eukaryotic translation initiation factor 4E (eIF4E) is induced during T cell activation and, in turn, regulates translation of cell cycle related mRNAs and proliferation in both T(Foxp3)- and T(Foxp3+) cells. Unexpectedly, eIF4E also affects Foxp3 expression and thereby lineage identity. Thus, mRNA-specific translational control directs both common and distinct cellular processes in CD4(+) T cell subsets.
authors: Department of Microbiology and Immunology, McGill University, Montreal, Canada.
authors: Eva
authors: E
authors: Bjur
authors: Ola
authors: O
authors: Larsson
authors: Ekaterina
authors: E
authors: Yurchenko
authors: Lei
authors: L
authors: Zheng
authors: Valentina
authors: V
authors: Gandin
authors: Ivan
authors: I
authors: Topisirovic
authors: Shui
authors: S
authors: Li
authors: Carston R
authors: CR
authors: Wagner
authors: Nahum
authors: N
authors: Sonenberg
authors: Ciriaco A
authors: CA
authors: Piccirillo
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D039561:Eukaryotic Initiation Factor-4E; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger
references: Nat Immunol. 2009 Jul;10(7):689-95
references: 19536194
references: Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7797-802
references: 18509048
references: J Exp Med. 1998 Jul 20;188(2):287-96
references: 9670041
references: Immunol Rev. 2006 Aug;212:8-27
references: 16903903
references: Nucleic Acids Res. 2005 Nov 10;33(20):e175
references: 16284200
references: Blood. 2008 Sep 1;112(5):1557-69
references: 18725574
references: Proteomics Clin Appl. 2009 Jan;3(1):83-94
references: 21136938
references: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3107-12
references: 12626741
references: Nature. 2007 Feb 15;445(7129):771-5
references: 17220874
references: Nat Rev Genet. 2007 Jul;8(7):533-43
references: 17572691
references: FASEB J. 2000 Aug;14(11):1641-52
references: 10928999
references: Nucleic Acids Res. 2006;34(16):4375-86
references: 16936314
references: Nat Immunol. 2010 Jul;11(7):618-27
references: 20467422
references: Immunity. 2011 Jan 28;34(1):50-60
references: 21236706
references: Immunity. 2005 Mar;22(3):329-41
references: 15780990
references: Cancer Res. 2007 Jul 15;67(14):6814-24
references: 17638893
references: Nature. 2008 Mar 20;452(7185):323-8
references: 18272964
references: PLoS Biol. 2008 Oct 28;6(10):e255
references: 18959479
references: J Biol Chem. 2002 Jun 21;277(25):22175-84
references: 11943782
references: Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21487-92
references: 21115840
references: Nature. 2009 Nov 19;462(7271):358-62
references: 19924215
references: Bioinformatics. 2011 May 15;27(10):1440-1
references: 21422072
references: PLoS One. 2007 Feb 21;2(2):e242
references: 17311107
references: Bioinformatics. 2004 Dec 12;20(18):3710-5
references: 15297299
references: FASEB J. 1998 Mar;12(3):299-306
references: 9506473
references: Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5919-24
references: 20231436
references: Mol Cell Biol. 1999 Mar;19(3):1720-30
references: 10022859
references: J Clin Invest. 2002 Jul;110(1):119-26
references: 12093895
references: Mol Syst Biol. 2010 Aug 24;6:400
references: 20739923
references: Cell. 2008 May 30;133(5):775-87
references: 18510923
references: Cell. 2009 Feb 20;136(4):731-45
references: 19239892
references: Immunol Rev. 2009 May;229(1):41-66
references: 19426214
references: BMC Bioinformatics. 2009 May 27;10:161
references: 19473525
references: Cancer Res. 2009 Nov 1;69(21):8455-62
references: 19843855
references: Immunity. 2007 Nov;27(5):786-800
references: 18024188
references: Immunity. 2009 Jun 19;30(6):832-44
references: 19538929
references: Immunity. 2009 May;30(5):646-55
references: 19464987
references: Mol Syst Biol. 2009;5:288
references: 19638969
references: Science. 2010 May 28;328(5982):1172-6
references: 20508131
references: Nature. 2011 May 19;473(7347):337-42
references: 21593866
references: Toxicol Appl Pharmacol. 2011 Feb 15;251(1):8-15
references: 21092744
references: Nat Immunol. 2005 Nov;6(11):1142-51
references: 16227984
references: Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1649-54
references: 15668399
references: ACS Chem Biol. 2009 May 15;4(5):367-77
references: 19351181
references: J Biol Chem. 1992 Oct 5;267(28):20444-50
references: 1400363
references: Immunology. 2011 Feb;132(2):157-64
references: 21091910