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

doi:10.1182/blood-2005-02-0456

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 journal › Article › peer-review

76 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	879-885
Number of pages	7
Journal	Blood
Volume	106
Issue number	3
DOIs	https://doi.org/10.1182/blood-2005-02-0456
Publication status	Published - Aug 1 2005
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Immunology
Hematology
Cell Biology

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10.1182/blood-2005-02-0456

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title = "IL-6 blocks a discrete early step in lymphopoiesis",

abstract = "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.",

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

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T1 - IL-6 blocks a discrete early step in lymphopoiesis

AU - Maeda, Kazuhiko

AU - Baba, Yoshihiro

AU - Nagai, Yoshinori

AU - Miyazaki, Kozo

AU - Malykhin, Alexander

AU - Nakamura, Koji

AU - Kincade, Paul W.

AU - Sakaguchi, Nobuo

AU - Coggeshall, K. Mark

PY - 2005/8/1

Y1 - 2005/8/1

N2 - 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.

AB - 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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JO - Blood

JF - Blood

IS - 3

ER -

IL-6 blocks a discrete early step in lymphopoiesis

Abstract

All Science Journal Classification (ASJC) codes

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