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Interleukin-27 directly induces differentiation in hematopoietic stem cells.

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.

Pubmed ID: 18042804

Authors

  • Seita J
  • Asakawa M
  • Ooehara J
  • Takayanagi S
  • Morita Y
  • Watanabe N
  • Fujita K
  • Kudo M
  • Mizuguchi J
  • Ema H
  • Nakauchi H
  • Yoshimoto T

Journal

Blood

Publication Data

February 15, 2008

Associated Grants

None

Mesh Terms

  • Animals
  • Antigens, CD34
  • Bone Marrow Cells
  • Cell Differentiation
  • DNA Primers
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
  • Hematopoietic Stem Cells
  • Humans
  • Interleukins
  • Mice
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction