白细胞介素-6阻断淋巴细胞生成过程中一个特定的早期步骤。
IL-6 blocks a discrete early step in lymphopoiesis.
作者信息
Maeda Kazuhiko, Baba Yoshihiro, Nagai Yoshinori, Miyazaki Kozo, Malykhin Alexander, Nakamura Koji, Kincade Paul W, Sakaguchi Nobuo, Coggeshall K Mark
机构信息
Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, 825 NE 13th St, Oklahoma City, OK 73104, USA.
出版信息
Blood. 2005 Aug 1;106(3):879-85. doi: 10.1182/blood-2005-02-0456. Epub 2005 Apr 14.
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.
摘要
缺乏含Src同源2结构域的肌醇5 -磷酸酶（SHIP）的动物，其淋巴细胞生成减少，而骨髓生成相应增强。这些效应至少部分是由白细胞介素6（IL - 6）水平升高介导的。在此，我们表明SHIP基因敲除小鼠中的淋巴细胞生成阻滞是由于未定向祖细胞对淋巴系选择的抑制。这种抑制在体外可通过重组IL - 6重现，且IL - 6直接作用于造血祖细胞。在SHIP基因敲除/IL - 6基因敲除双缺陷动物中，这种阻滞部分得到克服。IL - 6并不抑制而是实际上增强淋巴定向祖细胞的增殖，表明IL - 6的靶细胞是造血干细胞或多能祖细胞。这些发现提示了一种伴随促炎疾病出现的淋巴细胞减少的机制。
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