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Blood, 1 August 2005, Vol. 106, No. 3, pp. 879-885.
Prepublished online as a Blood First Edition Paper on April 14, 2005; DOI 10.1182/blood-2005-02-0456.


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HEMATOPOIESIS

IL-6 blocks a discrete early step in lymphopoiesis

Kazuhiko Maeda, Yoshihiro Baba, Yoshinori Nagai, Kozo Miyazaki, Alexander Malykhin, Koji Nakamura, Paul W. Kincade, Nobuo Sakaguchi, and K. Mark Coggeshall

From the Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; and Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, Japan.

Animals lacking Src homology 2 domain-containing inositol 5-phosphatase (SHIP) display a reduction in lymphopoiesis and a corresponding enhancement of myelopoiesis. These effects are mediated at least in part by elevated levels of interleukin 6 (IL-6). Here, we show the lymphopoiesis block in SHIP–/– mice is due to suppression of the lymphoid lineage choice by uncommitted progenitors. The suppression can be reproduced in vitro with recombinant IL-6, and IL-6 acts directly on hematopoietic progenitors. The block is partially overcome in SHIP–/– IL-6–/– double-deficient animals. IL-6 does not suppress but actually enhances proliferation of lymphoid-committed progenitors, indicating the IL-6 target cells are hematopoietic stem cells or multipotent progenitors. The findings suggest a mechanism for the lymphopenia that accompanies proinflammatory diseases.


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