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Transcriptional regulation of IL-15 expression during hematopoiesis.


ABSTRACT: 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.

SUBMITTER: Colpitts SL 

PROVIDER: S-EPMC3896262 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Transcriptional regulation of IL-15 expression during hematopoiesis.

Colpitts Sara L SL   Stonier Spencer W SW   Stoklasek Thomas A TA   Root Sierra H SH   Aguila Hector Leonardo HL   Schluns Kimberly S KS   Lefrançois Leo L  

Journal of immunology (Baltimore, Md. : 1950) 20130821 6


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 lineage  ...[more]

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