title: 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.
authors: Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Sara L
authors: SL
authors: Colpitts
authors: Spencer W
authors: SW
authors: Stonier
authors: Thomas A
authors: TA
authors: Stoklasek
authors: Sierra H
authors: SH
authors: Root
authors: Hector Leonardo
authors: HL
authors: Aguila
authors: Kimberly S
authors: KS
authors: Schluns
authors: Leo
authors: L
authors: Lefrançois
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage; D002469:Cell Separation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006410:Hematopoiesis / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D019409:Interleukin-15
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