Ets-1, a functional cofactor of T-bet, is essential for Th1 inflammatory responses

被引:101
作者
Grenningloh, K
Kang, BY
Ho, IC
机构
[1] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
关键词
D O I
10.1084/jem.20041330
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To mount an effective type 1 immune response, type 1 T helper (Th1) cells must produce inflammatory cytokines and simultaneously suppress the expression of antiinflammatory cytokines. How these two processes are coordinately regulated at the molecular level is still unclear. In this paper, we show that the proto-oncogene E26 transformation-specific-1 (Ets-1) is necessary for T-bet to promote interferon-gamma production and that Ets-1 is essential for mounting effective Th1 inflammatory responses in vivo. In addition, Ets-1-deficient Th1 cells also produce a very high level of interleukin 10. Thus, Ill plays a crucial and unique role in the reciprocal regulation of inflammatory and antiinflammatory Th responses.
引用
收藏
页码:615 / 626
页数:12
相关论文
共 51 条
  • [1] T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells
    Afkarian, M
    Sedy, JR
    Yang, J
    Jacobson, NG
    Cereb, N
    Yang, SY
    Murphy, TL
    Murphy, KM
    [J]. NATURE IMMUNOLOGY, 2002, 3 (06) : 549 - 557
  • [2] An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation
    Asseman, C
    Mauze, S
    Leach, MW
    Coffman, RL
    Powrie, F
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (07) : 995 - 1003
  • [3] Control of experimental inflammatory bowel disease by regulatory T cells
    Asseman, C
    Fowler, S
    Powrie, F
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 162 (04) : S185 - +
  • [4] The Ets-1 transcription factor is required for the development of natural killer cells in mice
    Barton, K
    Muthusamy, N
    Fischer, C
    Ting, CN
    Walunas, TL
    Lanier, LL
    Leiden, JM
    [J]. IMMUNITY, 1998, 9 (04) : 555 - 563
  • [5] Physical interactions between ets and NF-kappa B/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells
    Bassuk, AG
    Anandappa, RT
    Leiden, JM
    [J]. JOURNAL OF VIROLOGY, 1997, 71 (05) : 3563 - 3573
  • [6] RECIPROCAL EXPRESSION OF HUMAN ETS1 AND ETS2 GENES DURING T-CELL ACTIVATION - REGULATORY ROLE FOR THE PROTOONCOGENE ETS1
    BHAT, NK
    THOMPSON, CB
    LINDSTEN, T
    JUNE, CH
    FUJIWARA, S
    KOIZUMI, S
    FISHER, RJ
    PAPAS, TS
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (10) : 3723 - 3727
  • [7] BHAT NK, 1989, J IMMUNOL, V142, P672
  • [8] Regulation of the human interleukin-5 promoter by Ets transcription factors -: Ets1 and Ets2, but not Elf-1, cooperate with GATA3 and HTLV-I Tax1
    Blumenthal, SG
    Aichele, G
    Wirth, T
    Czernilofsky, AP
    Nordheim, A
    Dittmer, J
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (18) : 12910 - 12916
  • [9] INCREASED T-CELL APOPTOSIS AND TERMINAL B-CELL DIFFERENTIATION-INDUCED BY INACTIVATION OF THE ETS-1 PROTOONCOGENE
    BORIES, JC
    WILLERFORD, DM
    GREVIN, D
    DAVIDSON, L
    CAMUS, A
    MARTIN, P
    STEHELIN, D
    ALT, FW
    [J]. NATURE, 1995, 377 (6550) : 635 - 638
  • [10] c-Myc target gene specificity is determined by a post-DNA-binding mechanism
    Boyd, KE
    Wells, J
    Gutman, J
    Bartley, SM
    Farnham, PJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (23) : 13887 - 13892