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, K. Mark Coggeshall

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)879-885
Number of pages7
Issue number3
Publication statusPublished - Aug 1 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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