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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1903-1912. Prepublished online as a Blood First Edition Paper on November 27, 2007; DOI 10.1182/blood-2007-06-093328. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-06-093328v1 111/4/1903    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Seita, J. Articles by Yoshimoto, T. Search for Related Content PubMed PubMed Citation Articles by Seita, J. Articles by Yoshimoto, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 19, 2007 Accepted November 9, 2007 Interleukin-27 directly induces differentiation in hematopoietic stem cells Jun Seita, Masayuki Asakawa, Jun Ooehara, Shin-ichiro Takayanagi, Yohei Morita, Nobukazu Watanabe, Koji Fujita, Motoshige Kudo, Junichiro Mizuguchi, Hideo Ema, Hiromitsu Nakauchi, and Takayuki Yoshimoto* Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo, Japan ReproCell, Tokyo, Japan Department of Pathology, Tokyo Medical University, Tokyo, Japan Department of Immunology, Tokyo Medical University, Tokyo, Japan * Corresponding author; email: yoshimot{at}tokyo-med.ac.jp. 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 -/lowc-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 was also 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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