期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 201, 期 11, 页码 1771-1780出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20041419
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资金
- NCI NIH HHS [CA-98129, R01 CA098129] Funding Source: Medline
- NIAID NIH HHS [AI-56123, AI-49326, R01 AI024335, AI-52077, AI-24335, U19 AI056363-010002, R01 AI049326, R01 AI056123, U19 AI056363, T32 AI052077, AI-56363, R01 AI024335-21] Funding Source: Medline
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.
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