| First Author | Taschner S | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 3 | Pages | 971-9 |
| PubMed ID | 17018855 | Mgi Jnum | J:144392 |
| Mgi Id | MGI:3830884 | Doi | 10.1182/blood-2006-04-020552 |
| Citation | Taschner S, et al. (2007) Down-regulation of RXRalpha expression is essential for neutrophil development from granulocyte/monocyte progenitors. Blood 109(3):971-9 |
| abstractText | Neutrophil granulocytes (Gs) represent highly abundant and short-lived leukocytes that are constantly regenerated from a small pool of myeloid committed progenitors. Nuclear receptor (NR) family members are ligand-activated transcription factors that play key roles in cellular proliferation and differentiation processes including myelopoiesis. Retinoid X receptor alpha (RXRalpha) represents the predominant NR types I and II homo- and heterodimerization partner in myeloid cells. Here we show that human myeloid progenitors express RXRalpha protein at sustained high levels during macrophage colony-stimulating factor (M-CSF)-induced monopoiesis. In sharp contrast, RXRalpha is down-regulated during G-CSF-dependent late-stage neutrophil differentiation from myeloid progenitors. Down-regulation of RXRalpha is critically required for neutrophil development since ectopic RXRalpha inhibited granulopoiesis by impairing proliferation and differentiation. Moreover, ectopic RXRalpha was sufficient to redirect G-CSF-dependent granulocyte differentiation to the monocyte lineage and to promote M-CSF-induced monopoiesis. Functional genetic interference with RXRalpha signaling in hematopoietic progenitor/stem cells using a dominant-negative RXRalpha promoted the generation of late-stage granulocytes in human cultures in vitro and in reconstituted mice in vivo. Therefore, our data suggest that RXRalpha down-regulation is a critical requirement for the generation of neutrophil granulocytes. |
