Transcriptional Regulation of IL-15 Expression during Hematopoiesis

被引:51
作者
Colpitts, Sara L. [1 ]
Stonier, Spencer W. [2 ]
Stoklasek, Thomas A. [1 ]
Root, Sierra H. [1 ]
Aguila, Hector Leonardo [1 ]
Schluns, Kimberly S. [2 ]
Lefrancois, Leo [1 ]
机构
[1] Univ Connecticut, Ctr Hlth, Dept Immunol, Farmington, CT 06030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77054 USA
基金
美国国家卫生研究院;
关键词
DENDRITIC CELL-DEVELOPMENT; NATURAL-KILLER-CELLS; CD8(+) T-CELLS; BONE-MARROW; TRANS-PRESENTATION; MEMORY PHENOTYPE; CUTTING EDGE; NK CELLS; ALPHA-CHAIN; FACTOR PU.1;
D O I
10.4049/jimmunol.1301389
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Dendritic cells (DCs) are the most commonly studied source of the cytokine IL-15. Using an IL-15 reporter transgenic mouse, we have recently shown previously unappreciated differences in the levels of IL-15 expressed by subsets of conventional DCs (CD8(+) and CD8(-)). In this study, we show that IL-15 promoter activity was differentially regulated in subsets of hematopoietically derived cells with IL-15 expression largely limited to myeloid lineages. In contrast, mature cells of the lymphoid lineages expressed little to no IL-15 activity. Surprisingly, we discovered that hematopoietic stem cells (lineage(-)Sca-1(+)c-Kit(+)) expressed high levels of IL-15, suggesting that IL-15 expression was extinguished during lymphoid development. In the case of T cells, this downregulation was Notch-dependent and occurred in a stepwise pattern coincident with increasing maturation and commitment to a T cell fate. Finally, we further demonstrate that IL-15 expression was also controlled throughout DC development, with key regulatory activity of IL-15 production occurring at the pre-DC branch point, leading to the generation of both IL-15(+)CD8(+) and IL-15(-/low) CD8(-) DC subsets. Thus, IL-15 expression is coordinated with cellular fate in myeloid versus lymphoid immune cells.
引用
收藏
页码:3017 / 3024
页数:8
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