| First Author | Seita J | Year | 2008 |
| Journal | Blood | Volume | 111 |
| Issue | 4 | Pages | 1903-12 |
| PubMed ID | 18042804 | Mgi Jnum | J:131333 |
| Mgi Id | MGI:3773505 | Doi | 10.1182/blood-2007-06-093328 |
| Citation | Seita J, et al. (2008) Interleukin-27 directly induces differentiation in hematopoietic stem cells. Blood 111(4):1903-12 |
| abstractText | Interleukin (IL)-27, one of the most recently discovered IL-6 family cytokines, activates both the signal transducer and activator of transcription (STAT)1 and STAT3, and plays multiple roles in pro- and anti-inflammatory immune responses. IL-27 acts on various types of cells including T, B, and macrophage through the common signal-transducing receptor gp130 and its specific receptor WSX-1, but the effect of IL-27 on hematopoietic stem cells (HSCs) remains unknown. Here, we show that IL-27 together with stem cell factor (SCF) directly acts on HSCs and supports their early differentiation in vitro and in vivo. CD34(-/low)c-Kit(+)Sca-1(+)lineage marker(-) (CD34(-)KSL) cells, a population highly enriched in mouse HSCs, were found to express both IL-27 receptor subunits. In vitro cultures of CD34(-)KSL cells with IL-27 and SCF resulted in an expansion of progenitors including short-term repopulating cells, while some of their long-term repopulating activity also was maintained. To examine its in vivo effect, transgenic mice expressing IL-27 were generated. These mice exhibited enhanced myelopoiesis and impaired B lymphopoiesis in the bone marrow with extramedullary hematopoiesis in the spleen. Moreover, IL-27 similarly acted on human CD34(+) cells. These results suggest that IL-27 is one of the limited cytokines that play a role in HSC regulation. |
