IL-6 blocks a discrete early step in lymphopoiesis.
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.
Maeda
Kazuhiko
K
Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, 825 NE 13th St, Oklahoma City, OK 73104, USA.
Baba
Yoshihiro
Y
Nagai
Yoshinori
Y
Miyazaki
Kozo
K
Malykhin
Alexander
A
Nakamura
Koji
K
Kincade
Paul W
PW
Sakaguchi
Nobuo
N
Coggeshall
K Mark
KM
D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D000072181:Inositol Polyphosphate 5-Phosphatases; D015850:Interleukin-6 / Q000172:deficiency / Q000502:physiology*; D008231:Lymphopenia / Q000209:etiology; D038041:Lymphopoiesis; D051379:Mice; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency / Q000502:physiology*
D015850:Interleukin-6; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases