Home LiteratureArticle Details
PMID: 14978277 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Kinetic analysis of genomewide gene expression reveals molecule circuitries that control T cell activation and Th1/2 differentiation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 9 ·2004-03-02 ·Pages 3023-8

Lu B, Zagouras P, Fischer JE, Lu J, Li B, Flavell RA

Abstract

The global gene expression profiling of early T helper (Th) 1 and Th2 differentiation reveals that this process can be divided into two stages, activation and differentiation. The activation stage is manifested in coordinated mobilization of the replication machinery, a process that we hypothesize may be responsible for establishing genomewide opening of transcription loci. The molecular programs underlying the differentiation stage consist of highly regulated expression of functional groups of genes that are important for the biological properties of Th1/2 cells and transcription factors that are likely important in establishing terminal differentiation of these cells. The kinetics of expression pattern of a number of transcription factors shed new light on the molecular events that shape the outcome of Th1/2 differentiation.

MeSH Terms
Cell Cycle Cell Differentiation/immunology Cell Division Cytokines/genetics Gene Expression Regulation/immunology Genome, Human Humans Lymphocyte Activation/immunology Receptors, Cytokine/genetics Th1 Cells/cytology,immunology Th2 Cells/cytology,immunology Transcription Factors/immunology Transcription, Genetic/immunology
Chemicals
Cytokines Receptors, Cytokine Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lu Binfeng
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. bifeng@pitt.edu
Zagouras Panayiotis
Fischer James E
Lu Junfeng
Li Baiyong
Flavell Richard A
References (66)
66 references, click to expand
  1. Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation.
    Immunity. 2002 May;16(5):733-44 PMID: 12049724
  2. Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T cells.
    J Exp Med. 2002 Jun 17;195(12):1515-22 PMID: 12070279
  3. Interferon gamma stabilizes the T helper cell type 1 phenotype.
    J Exp Med. 2001 Jul 16;194(2):165-72 PMID: 11457891
  4. IL-7 is critical for homeostatic proliferation and survival of naive T cells.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8732-7 PMID: 11447288
  5. E4BP4/NFIL3, a PAR-related bZIP factor with many roles.
    Bioessays. 2002 Nov;24(11):1023-9 PMID: 12386933
  6. Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells.
    J Exp Med. 2002 Jun 17;195(12):1523-32 PMID: 12070280
  7. Overexpression of interleukin (IL)-7 leads to IL-15-independent generation of memory phenotype CD8+ T cells.
    J Exp Med. 2002 Jun 17;195(12):1533-9 PMID: 12070281
  8. Multiple choices: regulation of memory CD8 T cell generation and homeostasis by interleukin (IL)-7 and IL-15.
    J Exp Med. 2002 Jun 17;195(12):F49-52 PMID: 12070294
  9. T(H) cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes.
    Nat Immunol. 2002 Jul;3(7):643-51 PMID: 12055628
  10. Cutting edge: changes in histone acetylation at the IL-4 and IFN-gamma loci accompany Th1/Th2 differentiation.
    J Immunol. 2002 Jul 15;169(2):647-50 PMID: 12097365
  11. Subsets of CD4 T cells and B cell activation.
    Semin Immunol. 1989 Sep;1(1):21-31 PMID: 15630956
  12. IFN consensus sequence binding protein potentiates STAT1-dependent activation of IFNgamma-responsive promoters in macrophages.
    Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):91-6 PMID: 10618376
  13. Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment.
    Immunity. 2000 Jan;12(1):27-37 PMID: 10661403
  14. A novel transcription factor, T-bet, directs Th1 lineage commitment.
    Cell. 2000 Mar 17;100(6):655-69 PMID: 10761931
  15. Transcript imaging of the development of human T helper cells using oligonucleotide arrays.
    Nat Genet. 2000 May;25(1):96-101 PMID: 10802665
  16. The transcription factor EPAS-1/hypoxia-inducible factor 2alpha plays an important role in vascular remodeling.
    Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8386-91 PMID: 10880563
  17. Caspase-11 mediates oligodendrocyte cell death and pathogenesis of autoimmune-mediated demyelination.
    J Exp Med. 2001 Jan 1;193(1):111-22 PMID: 11136825
  18. An instructive component in T helper cell type 2 (Th2) development mediated by GATA-3.
    J Exp Med. 2001 Mar 5;193(5):643-50 PMID: 11238595
  19. Regulation of STRA13 by the von Hippel-Lindau tumor suppressor protein, hypoxia, and the UBC9/ubiquitin proteasome degradation pathway.
    J Biol Chem. 2001 May 4;276(18):15306-15 PMID: 11278694
  20. Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level.
    Immunity. 2001 Apr;14(4):447-59 PMID: 11336690
  21. GADD45gamma mediates the activation of the p38 and JNK MAP kinase pathways and cytokine production in effector TH1 cells.
    Immunity. 2001 May;14(5):583-90 PMID: 11371360
  22. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection.
    Science. 2001 Jun 8;292(5523):1907-10 PMID: 11397944
  23. Th2 cell-specific cytokine expression and allergen-induced airway inflammation depend on JunB.
    EMBO J. 2002 Dec 2;21(23):6321-9 PMID: 12456639
  24. Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes.
    J Biol Chem. 2002 Dec 6;277(49):47014-21 PMID: 12354771
  25. The lineage decisions of helper T cells.
    Nat Rev Immunol. 2002 Dec;2(12):933-44 PMID: 12461566
  26. Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development.
    Cell. 2002 Nov 27;111(5):621-33 PMID: 12464175
  27. Identification of RUNX1/AML1 as a classical tumor suppressor gene.
    Oncogene. 2003 Jan 30;22(4):538-47 PMID: 12555067
  28. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.
    J Immunol. 1986 Apr 1;136(7):2348-57 PMID: 2419430
  29. Cell growth cycle block of T cell hybridomas upon activation with antigen.
    J Exp Med. 1987 Jan 1;165(1):173-94 PMID: 3491868
  30. Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes.
    Nature. 1989 Jun 22;339(6226):625-6 PMID: 2786609
  31. Apoptotic phenotype induced by overexpression of wild-type gas3/PMP22: its relation to the demyelinating peripheral neuropathy CMT1A.
    Genes Dev. 1995 Aug 1;9(15):1846-56 PMID: 7649472
  32. Cloning of a new cytokine that induces IFN-gamma production by T cells.
    Nature. 1995 Nov 2;378(6552):88-91 PMID: 7477296
  33. Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells.
    J Exp Med. 1997 Mar 3;185(5):817-24 PMID: 9120387
  34. Control of inflammation, cytokine expression, and germinal center formation by BCL-6.
    Science. 1997 Apr 25;276(5312):589-92 PMID: 9110977
  35. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells.
    Cell. 1997 May 16;89(4):587-96 PMID: 9160750
  36. The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation.
    Nat Genet. 1997 Jun;16(2):161-70 PMID: 9171827
  37. IGIF does not drive Th1 development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NFkappaB.
    Immunity. 1997 Oct;7(4):571-81 PMID: 9354477
  38. Cyclin-dependent kinases: engines, clocks, and microprocessors.
    Annu Rev Cell Dev Biol. 1997;13:261-91 PMID: 9442875
  39. Redundant regulation of T cell differentiation and TCRalpha gene expression by the transcription factors LEF-1 and TCF-1.
    Immunity. 1998 Jan;8(1):11-20 PMID: 9462507
  40. The duration of antigenic stimulation determines the fate of naive and effector T cells.
    Immunity. 1998 Jan;8(1):89-95 PMID: 9462514
  41. Multiple gene duplication and expression of mouse bcl-2-related genes, A1.
    Int Immunol. 1998 May;10(5):631-7 PMID: 9645611
  42. Targeted disruption of the interferon-gamma receptor 2 gene results in severe immune defects in mice.
    Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8233-8 PMID: 9653170
  43. Mitochondria and apoptosis.
    Science. 1998 Aug 28;281(5381):1309-12 PMID: 9721092
  44. Helper T cell differentiation is controlled by the cell cycle.
    Immunity. 1998 Aug;9(2):229-37 PMID: 9729043
  45. GATA-3-dependent enhancer activity in IL-4 gene regulation.
    J Immunol. 1998 Oct 15;161(8):3822-6 PMID: 9780146
  46. Expressed genes in interleukin-4 treated B cells identified by cDNA representational difference analysis.
    Mol Immunol. 1998 Jun;35(8):487-502 PMID: 9798653
  47. Activation of blood T lymphocytes down-regulates CXCR4 expression and interferes with propagation of X4 HIV strains.
    Eur J Immunol. 1998 Oct;28(10):3192-204 PMID: 9808188
  48. T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6.
    Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13823-8 PMID: 9811885
  49. Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism.
    Immunity. 1998 Nov;9(5):745-55 PMID: 9846495
  50. Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation.
    EMBO J. 1999 Jan 15;18(2):420-32 PMID: 9889198
  51. Cyclins and cell cycle checkpoints.
    Annu Rev Pharmacol Toxicol. 1999;39:295-312 PMID: 10331086
  52. BCL-6-deficient mice reveal an IL-4-independent, STAT6-dependent pathway that controls susceptibility to infection by Leishmania major.
    J Immunol. 1999 Aug 15;163(4):2098-103 PMID: 10438949
  53. Expression of the transcription factor lung Krüppel-like factor is regulated by cytokines and correlates with survival of memory T cells in vitro and in vivo.
    J Immunol. 1999 Oct 1;163(7):3662-7 PMID: 10490960
  54. Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching.
    Mol Cell Biol. 1999 Oct;19(10):7264-75 PMID: 10490661
  55. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs.
    Cell. 1999 Oct 1;99(1):23-33 PMID: 10520991
  56. Gene microarrays reveal extensive differential gene expression in both CD4(+) and CD8(+) type 1 and type 2 T cells.
    J Immunol. 2001 Sep 15;167(6):3057-63 PMID: 11544289
  57. Defective T cell activation and autoimmune disorder in Stra13-deficient mice.
    Nat Immunol. 2001 Nov;2(11):1040-7 PMID: 11668339
  58. The interplay between Mad and Myc in proliferation and differentiation.
    Trends Cell Biol. 2001 Nov;11(11):S10-4 PMID: 11684436
  59. Friend of GATA-1 represses GATA-3-dependent activity in CD4+ T cells.
    J Exp Med. 2001 Nov 19;194(10):1461-71 PMID: 11714753
  60. c-Myc regulates mammalian body size by controlling cell number but not cell size.
    Nature. 2001 Dec 13;414(6865):768-73 PMID: 11742404
  61. Differential regulation of two alternatively spliced isoforms of hypoxia-inducible factor-1 alpha in activated T lymphocytes.
    J Biol Chem. 2001 Dec 28;276(52):48754-63 PMID: 11602577
  62. Cutting edge: STAT6 serves as a positive and negative regulator of gene expression in IL-4-stimulated B lymphocytes.
    J Immunol. 2002 Feb 1;168(3):996-1000 PMID: 11801631
  63. Txk, a member of nonreceptor tyrosine kinase of Tec family, acts as a Th1 cell-specific transcription factor and regulates IFN-gamma gene transcription.
    J Immunol. 2002 Mar 1;168(5):2365-70 PMID: 11859127
  64. Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1.
    Immunity. 2002 Feb;16(2):231-43 PMID: 11869684
  65. T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells.
    Nat Immunol. 2002 Jun;3(6):549-57 PMID: 12006974
  66. Signal transduction by the TGF-beta superfamily.
    Science. 2002 May 31;296(5573):1646-7 PMID: 12040180
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0307743100
Email
bifeng@pitt.edu
Published
2004-03-02
Epub
2004-00-20
Pages
3023-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC365738
Subset
IM
Grants
NIAMS NIH HHS · K01 AR048854 · United States
NIAID NIH HHS · P01 AI036529 · United States
NIAMS NIH HHS · 1 K01 AR048854 · United States
NIAID NIH HHS · 1 P01 AI36529 · United States
External Links
PubMed source DOI: 10.1073/pnas.0307743100 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2