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胸腺肌样细胞保护胸腺细胞免于凋亡并调节其分化:ERK和Akt信号通路的作用

Thymic myoid cells protect thymocytes from apoptosis and modulate their differentiation: implication of the ERK and Akt signaling pathways.

作者信息

Le Panse R, Berrih-Aknin S

机构信息

CNRS UMR 8078, IPSC, Université Paris XI, Hôpital Marie Lannelongue, Le Plessis-Robinson, France.

出版信息

Cell Death Differ. 2005 May;12(5):463-72. doi: 10.1038/sj.cdd.4401611.

Abstract

Thymic myoid cells correspond to a muscle-like cell population present in the thymic medulla. They are well conserved throughout species evolution, but their biological role is not known. We demonstrated that myoid cells protected thymocytes from apoptosis as evidenced by a strong decrease of annexin-V-FITC positive thymocytes. This effect was (1) specific of myoid cells compared to thymic epithelial cells; (2) dependent on direct cell-to-cell contacts and (3) triggered rapidly after 2 h in cocultures. This protective phenomenon was due to the activation of prosurvival mechanisms. Indeed, myoid cells activated extracellular-regulated kinases (ERK1/2) and Akt in thymocytes. Myoid cells also influenced thymocyte maturation. We observed an increase in CD4(+) and a decrease in CD8(+) single positive (SP) thymocytes when cocultured with myoid cells, independently of a CD8(+)SP increased death or a CD4(+)SP overproliferation. Consequently, thymic myoid cells protect thymocytes from apoptosis and could also modulate their differentiation process.

摘要

胸腺肌样细胞对应于存在于胸腺髓质中的一类肌肉样细胞群体。它们在整个物种进化过程中高度保守,但其生物学作用尚不清楚。我们证明,肌样细胞可保护胸腺细胞免于凋亡,膜联蛋白-V-异硫氰酸荧光素(annexin-V-FITC)阳性胸腺细胞显著减少即证明了这一点。这种效应具有以下特点:(1)与胸腺上皮细胞相比,是肌样细胞所特有的;(2)依赖于细胞间的直接接触;(3)在共培养2小时后迅速触发。这种保护现象是由于促生存机制的激活。实际上,肌样细胞激活了胸腺细胞中的细胞外调节激酶(ERK1/2)和Akt。肌样细胞还影响胸腺细胞的成熟。当与肌样细胞共培养时,我们观察到CD4(+)单阳性(SP)胸腺细胞增加,CD8(+)SP胸腺细胞减少,这与CD8(+)SP死亡增加或CD4(+)SP过度增殖无关。因此,胸腺肌样细胞可保护胸腺细胞免于凋亡,并且还可能调节其分化过程。

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