共 42 条
Coreceptor gene imprinting governs thymocyte lineage fate
被引:24
作者:
Adoro, Stanley
[1
,2
]
McCaughtry, Thomas
[1
]
Erman, Batu
[3
]
Alag, Amala
[1
]
Van Laethem, Francois
[1
]
Park, Jung-Hyun
[1
]
Tai, Xuguang
[1
]
Kimura, Motoko
[1
]
Wang, Lie
[4
]
Grinberg, Alex
[5
]
Kubo, Masato
[6
]
Bosselut, Remy
[4
]
Love, Paul
[5
]
Singer, Alfred
[1
]
机构:
[1] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA
[2] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA
[3] Sabanci Univ, Fac Engn & Nat Sci, Biol Sci & Bioengn Program, Istanbul, Turkey
[4] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA
[5] NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA
[6] Tokyo Univ Sci, Div Biotechnol, Res Inst Biol Sci, Chiba, Japan
基金:
美国国家卫生研究院;
关键词:
coreceptor;
lineage fate;
Runx3;
ThPOK;
thymocyte development;
T-CELL DEVELOPMENT;
LYMPHOCYTE DEVELOPMENT;
TRANSCRIPTION FACTORS;
POSITIVE SELECTION;
TRANSGENIC MICE;
CD8;
EXPRESSION;
RUNX PROTEINS;
REGULATES CD4;
B-CELLS;
DIFFERENTIATION;
D O I:
10.1038/emboj.2011.388
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Immature thymocytes are bipotential cells that are signalled during positive selection to become either helper- or cytotoxic-lineage T cells. By tracking expression of lineage determining transcription factors during positive selection, we now report that the Cd8 coreceptor gene locus co-opts any coreceptor protein encoded within it to induce thymocytes to express the cytotoxic-lineage factor Runx3 and to adopt the cytotoxic-lineage fate, findings we refer to as 'coreceptor gene imprinting'. Specifically, encoding CD4 proteins in the endogenous Cd8 gene locus caused major histocompatibility complex class II-specific thymocytes to express Runx3 during positive selection and to differentiate into CD4(+) cytotoxic-lineage T cells. Our findings further indicate that coreceptor gene imprinting derives from the dynamic regulation of specific cis Cd8 gene enhancer elements by positive selection signals in the thymus. Thus, for coreceptor-dependent thymocytes, lineage fate is determined by Cd4 and Cd8 coreceptor gene loci and not by the specificity of T-cell antigen receptor/coreceptor signalling. This study identifies coreceptor gene imprinting as a critical determinant of lineage fate determination in the thymus. The EMBO Journal (2012) 31, 366-377. doi:10.1038/emboj.2011.388; Published online 28 October 2011
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页码:366 / 377
页数:12
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