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
引用
收藏
页码:366 / 377
页数:12
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