生物
细胞生物学
免疫系统
造血
树突状细胞
细胞因子
转录因子
免疫学
平衡
T细胞
效应器
信号转导
干细胞
遗传学
基因
作者
Lianne van de Laar,Paul J. Coffer,Andrea M. Woltman
出处
期刊:Blood
[American Society of Hematology]
日期:2012-04-12
卷期号:119 (15): 3383-3393
被引量:276
标识
DOI:10.1182/blood-2011-11-370130
摘要
Dendritic cells (DCs) represent a small and heterogeneous fraction of the hematopoietic system, specialized in antigen capture, processing, and presentation. The different DC subsets act as sentinels throughout the body and perform a key role in the induction of immunogenic as well as tolerogenic immune responses. Because of their limited lifespan, continuous replenishment of DC is required. Whereas the importance of GM-CSF in regulating DC homeostasis has long been underestimated, this cytokine is currently considered a critical factor for DC development under both steady-state and inflammatory conditions. Regulation of cellular actions by GM-CSF depends on the activation of intracellular signaling modules, including JAK/STAT, MAPK, PI3K, and canonical NF-κB. By directing the activity of transcription factors and other cellular effector proteins, these pathways influence differentiation, survival and/or proliferation of uncommitted hematopoietic progenitors, and DC subset–specific precursors, thereby contributing to specific aspects of DC subset development. The specific intracellular events resulting from GM-CSF–induced signaling provide a molecular explanation for GM-CSF–dependent subset distribution as well as clues to the specific characteristics and functions of GM-CSF–differentiated DCs compared with DCs generated by fms-related tyrosine kinase 3 ligand. This knowledge can be used to identify therapeutic targets to improve GM-CSF–dependent DC-based strategies to regulate immunity.
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