Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells
Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells
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DOI：
10.1182/blood-2006-10-049767
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发表时间：
2007-05-01
期刊：
影响因子：
20.3
通讯作者：
Hollaender, Georg A.
中科院分区：
文献类型：
--
作者：
Rossi, Simona W.;Jeker, Lukas T.;Hollaender, Georg A.
角质细胞生长因子（KGF）的全身给药可增强正常小鼠和接受骨髓移植小鼠的T细胞淋巴细胞生成。KGF可保护胸腺基质细胞免受细胞清除性条件反射和移植物抗宿主病诱导的损伤。然而，关于KGF对胸腺基质细胞作用的分子和细胞机制知之甚少。在这里，我们报告说，KGF诱导在体内的成熟和未成熟的胸腺上皮细胞（TECs）的瞬时扩张，并促进后者类型的细胞的分化。增加的TEC数在2周内恢复到正常值，微环境显示正常的结构组织。间质的变化启动未成熟胸腺细胞的扩增，并允许T细胞以增加的速率和延长的时间段正常发育。TEC中的KGF信号传导激活p53和NF-κ B途径，并导致TEC功能和T细胞发育所必需的几种靶基因的转录，包括骨形态发生蛋白2（BMP 2）、BMP 4、Wnt 5 B和Wnt 10 B。通过经典BMP途径的信号传导对于KGF作用至关重要。总之，这些数据为外源性KGF对TEC功能和胸腺生成的作用机制提供了新的见解。(C)2007年，美国血液学会。
The systemic administration of keratinocyte growth factor (KGF) enhances T-cell lymphopoiesis in normal mice and mice that received a bone marrow transplant. KGF exerts protection to thymic stromal cells from cytoablative conditioning and graft-versus-host disease-induced injury. However, little is known regarding KGF's molecular and cellular mechanisms of action on thymic stromal cells. Here, we report that KGF induces in vivo a transient expansion of both mature and immature thymic epithelial cells (TECs) and promotes the differentiation of the latter type of cells. The increased TEC numbers return within 2 weeks to normal values and the microenvironment displays a normal architectural organization. Stromal changes initiate an expansion of immature thymocytes and permit regular T-cell development at an increased rate and for an extended period of time. KGF signaling in TECs activates both the p53 and NF-kappa B pathways and results in the transcription of several target genes necessary for TEC function and T-cell development, including bone morphogenetic protein 2 (BMP2), BMP4, Wnt5b, and Wnt10b. Signaling via the canonical BMP pathway is critical for the KGF effects. Taken together, these data provide new insights into the mechanism(s) of action of exogenous KGF on TEC function and thymopoiesis. (C) 2007 by The American Society of Hematology.