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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.
HEMATOPOIESIS IL-6 blocks a discrete early step in lymphopoiesisFrom 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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