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

被引:222
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 [J].
Afkarian, M ;
Sedy, JR ;
Yang, J ;
Jacobson, NG ;
Cereb, N ;
Yang, SY ;
Murphy, TL ;
Murphy, KM .
NATURE IMMUNOLOGY, 2002, 3 (06) :549-557
[2]   LIGAND-INDUCED AUTOREGULATION OF IFN-GAMMA RECEPTOR-BETA CHAIN EXPRESSION IN T-HELPER CELL SUBSETS [J].
BACH, EA ;
SZABO, SJ ;
DIGHE, AS ;
ASHKENAZI, A ;
AGUET, M ;
MURPHY, KM ;
SCHREIBER, RD .
SCIENCE, 1995, 270 (5239) :1215-1218
[3]   MicroRNAs modulate hematopoietic lineage differentiation [J].
Chen, CZ ;
Li, L ;
Lodish, HF ;
Bartel, DP .
SCIENCE, 2004, 303 (5654) :83-86
[4]   T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer [J].
Cobb, BS ;
Nesterova, TB ;
Thompson, E ;
Hertweck, A ;
O'Connor, E ;
Godwin, J ;
Wilson, CB ;
Brockdorff, N ;
Fisher, AG ;
Smale, ST ;
Merkenschlager, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (09) :1367-1373
[5]   Accumulation of miR-155 and BIC RNA in human B cell lymphomas [J].
Eis, PS ;
Tam, W ;
Sun, LP ;
Chadburn, A ;
Li, ZD ;
Gomez, MF ;
Lund, E ;
Dahlberg, JE .
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 [J].
Haasch, D ;
Chen, YW ;
Reilly, RM ;
Chiou, XG ;
Koterski, S ;
Smith, ML ;
Kroeger, P ;
McWeeny, K ;
Halbert, DN ;
Mollison, KW ;
Djuric, SW ;
Trevillyan, JM .
CELLULAR IMMUNOLOGY, 2002, 217 (1-2) :78-86
[8]   A microRNA polycistron as a potential human oncogene [J].
He, L ;
Thomson, JM ;
Hemann, MT ;
Hernando-Monge, E ;
Mu, D ;
Goodson, S ;
Powers, S ;
Cordon-Cardo, C ;
Lowe, SW ;
Hannon, GJ ;
Hammond, SM .
NATURE, 2005, 435 (7043) :828-833
[9]  
HO CI, 1996, CELL, V85, P973
[10]   Gene regulation by transcription factors and microRNAs [J].
Hobert, Oliver .
SCIENCE, 2008, 319 (5871) :1785-1786