| First Author | Colpitts SL | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 6 | Pages | 3017-24 |
| PubMed ID | 23966624 | Mgi Jnum | J:205859 |
| Mgi Id | MGI:5546544 | Doi | 10.4049/jimmunol.1301389 |
| Citation | Colpitts SL, et al. (2013) Transcriptional regulation of IL-15 expression during hematopoiesis. J Immunol 191(6):3017-24 |
| abstractText | 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. |
