Micro-RNA-155 inhibits IFN-γ signaling in CD4+ T cells

被引:218
作者
Banerjee, Arnob [1 ,2 ]
Schambach, Felix [1 ,2 ]
DeJong, Caitlin S. [1 ,2 ]
Hammond, Scott M. [3 ]
Reiner, Steven L. [1 ,2 ]
机构
[1] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Med, Philadelphia, PA 19104 USA
[3] Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC USA
基金
美国国家卫生研究院;
关键词
CD4(+) T Cells; Cell differentiation; Cytokines; RECEPTOR-BETA CHAIN; INTERFERON-GAMMA; DIFFERENTIATION; EXPRESSION; MICRORNAS; EFFECTOR; MIR-155; ABSENCE; NAIVE; DICER;
D O I
10.1002/eji.200939381
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Micro-RNA (miR) are increasingly recognized as critical regulators of tissue-specific patterns of gene expression. CD4(+) T cells lacking miR-155, for example, exhibit bias towards Th2 differentiation, indicating that the absence of individual miR could alter CD4(+) T-cell differentiation. We now show that miR-155 is induced upon T-cell activation and that it promotes Th1 differentiation when over-expressed in activated CD4(+) T cells. Antagonism of miR-155 leads to induction of IFN-gamma receptor alpha-chain (IFN-gamma R alpha, and a functional miR-155 target site is identified within the 3' untranslated region of IFN-gamma R alpha. These results identify IFN-gamma R alpha as a second miR-155 target in T cells and suggest that miR-155 contributes to Th1 differentiation in CD4(+) T cells by inhibiting IFN-gamma signaling.
引用
收藏
页码:225 / 231
页数:7
相关论文
共 29 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] LIGAND-INDUCED AUTOREGULATION OF IFN-GAMMA RECEPTOR-BETA CHAIN EXPRESSION IN T-HELPER CELL SUBSETS
    BACH, EA
    SZABO, SJ
    DIGHE, AS
    ASHKENAZI, A
    AGUET, M
    MURPHY, KM
    SCHREIBER, RD
    [J]. SCIENCE, 1995, 270 (5239) : 1215 - 1218
  • [3] MicroRNAs modulate hematopoietic lineage differentiation
    Chen, CZ
    Li, L
    Lodish, HF
    Bartel, DP
    [J]. SCIENCE, 2004, 303 (5654) : 83 - 86
  • [4] T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer
    Cobb, BS
    Nesterova, TB
    Thompson, E
    Hertweck, A
    O'Connor, E
    Godwin, J
    Wilson, CB
    Brockdorff, N
    Fisher, AG
    Smale, ST
    Merkenschlager, M
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (09) : 1367 - 1373
  • [5] Accumulation of miR-155 and BIC RNA in human B cell lymphomas
    Eis, PS
    Tam, W
    Sun, LP
    Chadburn, A
    Li, ZD
    Gomez, MF
    Lund, E
    Dahlberg, JE
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (10) : 3627 - 3632
  • [6] GAJEWSKI TF, 1988, J IMMUNOL, V140, P4245
  • [7] T cell activation induces a noncoding RNA transcript sensitive to inhibition by immunosuppressant drugs and encoded by the proto-oncogene, BIC
    Haasch, D
    Chen, YW
    Reilly, RM
    Chiou, XG
    Koterski, S
    Smith, ML
    Kroeger, P
    McWeeny, K
    Halbert, DN
    Mollison, KW
    Djuric, SW
    Trevillyan, JM
    [J]. CELLULAR IMMUNOLOGY, 2002, 217 (1-2) : 78 - 86
  • [8] A microRNA polycistron as a potential human oncogene
    He, L
    Thomson, JM
    Hemann, MT
    Hernando-Monge, E
    Mu, D
    Goodson, S
    Powers, S
    Cordon-Cardo, C
    Lowe, SW
    Hannon, GJ
    Hammond, SM
    [J]. NATURE, 2005, 435 (7043) : 828 - 833
  • [9] HO CI, 1996, CELL, V85, P973
  • [10] Gene regulation by transcription factors and microRNAs
    Hobert, Oliver
    [J]. SCIENCE, 2008, 319 (5871) : 1785 - 1786