Ueda Yoshihiro, Kondo Motonari, Kelsoe Garnett
Department of Immunology, Duke University, Durham, NC 27710, USA.
J Exp Med. 2005 Jun 6;201(11):1771-80. doi: 10.1084/jem.20041419.
The coordinated production of leukocytes in bone marrow is crucial for innate and adaptive immunity. Inflammation alters normal leukocyte production by promoting granulopoiesis over lymphopoiesis, a response that supports the reactive neutrophilia that follows infection. Here we demonstrate that this specialization for granulopoiesis is determined by inflammation-induced reductions of growth and retention factors, most significantly stem cell factor and CXCL12, which act preferentially to inhibit lymphoid development. These hierarchical effects suggest that the normal equilibrium of leukocyte production in bone marrow is determined by lymphopoiesis' higher demand for specific growth factors and/or retention signals. Inflammation regulates this balance by reducing growth factors that have less impact on developing neutrophils than lymphocytes. We demonstrate that granulopoiesis and lymphopoiesis are coupled specifically in the bone marrow by development in a common niche and propose that the leukopoietic equilibrium is specified by limiting amounts of developmental resources.
骨髓中白细胞的协同产生对于先天性和适应性免疫至关重要。炎症通过促进粒细胞生成而非淋巴细胞生成来改变正常的白细胞产生，这种反应支持感染后出现的反应性中性粒细胞增多。在这里，我们证明粒细胞生成的这种特化是由炎症诱导的生长和保留因子减少所决定的，最显著的是干细胞因子和CXCL12，它们优先作用于抑制淋巴细胞发育。这些层级效应表明，骨髓中白细胞产生的正常平衡是由淋巴细胞生成对特定生长因子和/或保留信号的更高需求所决定的。炎症通过减少对发育中的中性粒细胞影响小于淋巴细胞的生长因子来调节这种平衡。我们证明粒细胞生成和淋巴细胞生成在骨髓中通过在共同生态位中的发育而特异性耦合，并提出白细胞生成平衡是由有限数量的发育资源所决定的。
