Regulation of thymic epithelium by keratinocyte growth factor
Regulation of thymic epithelium by keratinocyte growth factor
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DOI：
10.1182/blood-2002-04-1036
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发表时间：
2002-11-01
期刊：
影响因子：
20.3
通讯作者：
Farr, AG
中科院分区：
文献类型：
--
作者：
Erickson, M;Morkowski, S;Farr, AG
在这里，我们证明，角质形成细胞生长因子（KGF）和FGFR 2 IIIb信号可以影响胸腺上皮（TE）的发育和功能，以及α-谱系胸腺细胞有助于胸腺内的KGF水平。KGF的胸腺细胞表达受发育调节，在CD 3（-）4（-）8（-）胸腺细胞中检测不到，而在成熟的CD 4或CD 8胸腺细胞中表达最高水平。将胸腺细胞耗竭的胎儿胸腺叶暴露于KGF导致参与胸腺细胞阳性选择的II类主要组织相容性复合物（MHC）、不变链（li）和组织蛋白酶L（CatL）分子的胸腺上皮表达减少，并且还刺激细胞因子白细胞介素6（IL-6）和胸腺基质源性淋巴细胞生成素（TSLP）的表达，而对IL-7或干细胞因子表达几乎没有影响。在完整的胎儿胸腺器官培养（FTOC）中，外源性KGF损害CD 4胸腺细胞的产生。两条证据表明，髓TE室对KGF和FGFR 2 IIIb信号传导的反应性。首先，在体外暴露于KGF的完整FTOC中，髓室扩张。第二，在RAG缺陷的胸腺，胸腺细胞不表达可检测水平的KGF消息，发育不良的髓质TE室可以通过在体内施用重组KGF来扩大。这种扩张伴随着RAG 2（-/-）胸腺中髓质TE相关趋化因子表达的正常分布的恢复。总的来说，这些发现表明KGF和FGFR信号在胸腺上皮的发育和功能中的作用。(C)2002年，美国血液学会。
Here we demonstrate that keratinocyte growth factor (KGF) and FGFR2IIIb signaling can affect development and function of thymic epithelium (TE) and that alphabeta-lineage thymocytes contribute to intrathymic levels of KGF. Thymocyte expression of KGF is developmentally regulated, being undetectable in CD3(-)4(-)8(-) thymocytes and expressed at highest levels by mature CD4 or CD8 thymocytes. Exposure of thymocyte-depleted fetal thymic lobes to KGF resulted in reduced thymic epithelial expression of class II major histocompatibility complex (MHC), invariant chain (li), and cathepsin L (CatL) molecules involved in thymocyte-positive selection and also stimulated expression of the cytokines interleukin 6 (IL-6) and thymic stromal-derived lymphopoietin (TSLP), while having little effect on IL-7 or stem cell factor expression. Within intact fetal thymic organ culture (FTOC), exogenous KGF impairs the generation of CD4 thymocytes. Two lines of evidence point to responsiveness of the medullary TE compartment to KGF and FGFR2IIIb signaling. First, the medullary compartment is expanded in intact FTOC exposed to KGF in vitro. Second, in the RAG-deficient thymus, where the thymocytes do not express detectable levels of KGF message, the hypoplastic medullary TE compartment can be expanded by administration of recombinant KGF in vivo. This expansion is accompanied by restoration of the normal profile of medullary TE-associated chemokine expression in the RAG2(-/-) thymus. Collectively, these findings point to a role for KGF and FGFR signaling in the development and function of thymic epithelium. (C) 2002 by The American Society of Hematology.