Decreased expression of thymus-specific proteasome subunit β5t in Down syndrome patients.
Decreased expression of thymus-specific proteasome subunit β5t in Down syndrome patients.
复制标题
降低唐氏综合症患者胸腺特异性蛋白酶体亚基 β5t 的表达。
DOI：
10.1111/his.12642
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kasahara M.
中科院分区：
文献类型：
--
作者：
Tomaru U;Tsuji T;Kiuchi S;Ishizu A;Suzuki A;Otsuka N;Ito T;Ikeda H;Fukasawa Y;Kasahara M.
目的 大多数唐氏综合症 (DS)（21 三体）患者的胸腺形态异常，并存在主要影响细胞免疫反应的内在免疫异常。本研究的目的是检查 DS 患者胸腺基质细胞中功能重要分子的表达是否发生改变。方法和结果我们分析了 13 三体性 (n=4)、18 三体性 (n=14) 和 21 三体性 (n=13) 患者的胸腺组织的组织学改变，以及功能重要分子（如 β5t（一种胸腺蛋白酶体））的表达。 亚基、组织蛋白酶 L 和 S。13 三体和 18 三体患者的胸腺形态正常或仅显示皮质胸腺细胞轻度缺失。相比之下，21 三体患者的胸腺表现出不同的组织学变化。 13 例中有 6 例显示胸腺细胞严重耗竭，并伴有胸腺小叶结构消失。在此类胸腺中，梭形角蛋白阳性细胞密集分布，β5t 的表达显着降低，但组织蛋白酶 L 的表达没有显着降低。结论本研究表明，胸腺结构异常和胸腺基质细胞中功能重要分子的表达减少可能与 DS 患者的免疫学异常有关。
AimsThe majority of patients with Down syndrome (DS), trisomy 21, have morphologically abnormal thymuses and present with intrinsic immunological abnormalities affecting mainly the cellular immune response. The aim of this study was to examine whether the expression of functionally important molecules is altered in thymic stromal cells in patients with DS.Methods and resultsWe analysed thymic tissues from patients with trisomy 13 (n= 4), trisomy 18 (n= 14) and trisomy 21 (n= 13) for histological alterations, and for the expression of functionally important molecules such as β5t, a thymoproteasome subunit, and cathepsins L and S. In patients with trisomy 13 and trisomy 18, the thymus was morphologically normal or showed only mild depletion of cortical thymocytes. In contrast, the thymus showed variable histological changes in patients with trisomy 21; six of 13 cases showed severe depletion of thymocytes accompanied by the disappearance of thymic lobular architecture. In such thymuses, spindle‐shaped keratin‐positive cells were densely distributed, and expression of β5t, but not of cathepsin L, was markedly decreased.ConclusionsThe present study suggests that abnormal thymic architecture and decreased expression of functionally important molecules in thymic stromal cells may be involved in immunological abnormalities in DS patients.