Ontogeny of thymic cortical epithelial cells expressing the thymoproteasome subunit β5t

Ontogeny of thymic cortical epithelial cells expressing the thymoproteasome subunit β5t
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DOI:
10.1002/eji.201041375
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发表时间:
2011-04
影响因子:
5.4
通讯作者:
A. M. Ripen;T. Nitta;S. Murata;Keiji Tanaka;Y. Takahama
A. M. Ripen;T. Nitta;S. Murata;Keiji Tanaka;Y. Takahama
中科院分区:
医学3区
文献类型:
--
作者:
A. M. Ripen;T. Nitta;S. Murata;Keiji Tanaka;Y. Takahama

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蛋白酶体负责产生由免疫系统的I类MHC分子呈递的肽。β5t是一种最近发现的蛋白酶体成分,在胸腺皮质上皮细胞(cTEC)中特异性表达,并在产生I类MHC限制性CD8+ T细胞的免疫活性库中发挥关键作用。在这里,我们报告,β 5 t是检测胸腺早在E12.5小鼠胚胎。我们还发现,在RelB或Rag2缺陷的小鼠中,cTEC中的β5t表达是可检测的,这表明cTEC中的β5t在没有胸腺髓质形成或胸腺细胞发育超过CD4−CD8−阶段的情况下表达。在Foxn1缺陷裸鼠中未检测到胚胎胸腺中的β5t表达,尽管其表达在CCR7和CCR9缺陷的小鼠中未降低,其中白细胞的胎儿胸腺定殖是缺陷的。这些结果表明,β 5 t在cTECs中的表达依赖于Foxn1,但不依赖于胸腺细胞串扰或胸腺髓质形成。
Proteasomes are responsible for generating peptides presented by class I MHC molecules of the immune system. β5t, a recently identified proteasome component, is specifically expressed in thymic cortical epithelial cells (cTECs) and plays a pivotal role in generating an immunocompetent repertoire of class I MHC‐restricted CD8+ T cells. Here, we report that β5t is detectable in the thymus as early as E12.5 mouse embryos. We also found that β5t expression in cTECs was detectable in mice deficient for RelB or Rag2, indicating that β5t in cTECs is expressed in the absence of thymic medulla formation or thymocyte development beyond the CD4−CD8− stage. β5t expression in the embryonic thymus was not detectable in Foxn1‐deficient nude mice, although its expression was not reduced in mice deficient for both CCR7 and CCR9, in which fetal thymus colonization by leukocytes is defective. These results indicate that β5t expression in cTECs is dependent on Foxn1 but independent of thymocyte crosstalk or thymic medulla formation.