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.
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, 825 NE 13th St, Oklahoma City, OK 73104, USA.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Maeda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Baba
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nagai
authors.forename: Kozo
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Alexander
authors.initials: A
authors.lastname: Malykhin
authors.forename: Koji
authors.initials: K
authors.lastname: Nakamura
authors.forename: Paul W
authors.initials: PW
authors.lastname: Kincade
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakaguchi
authors.forename: K Mark
authors.initials: KM
authors.lastname: Coggeshall
mesh_terms: 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*
chemical_list: D015850:Interleukin-6; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases