Correction of autophagy impairment inhibits pathology in the NOD.H-2h4 mouse model of primary Sjögren's syndrome.
自噬损伤的纠正抑制 NOD 的病理。H-2h4 原发性干燥综合征的小鼠模型。

摘要

Dysregulation of autophagy has been implicated in the development of various disease indications including autoimmune diseases. Here we identified hitherto unsuspected molecular alterations of autophagy occurring at an early stage of the macroautophagy pathway in the salivary glands and spleen of NOD.H-2h4 mice that develop a primary Sjögren's-like syndrome. In this study we investigated the capacity of phosphopeptide P140 to correct immune alteration in NOD.H-2h4 mice and the effect on neogenesis of tertiary lymphoid structures in salivary glands, which is hallmark characteristic of SS. Phosphopeptide P140 known to lower excessive autophagy processes, rescued sick NOD.H-2h4 mice from some autophagy defects and significantly reduced formation of tertiary lymphoid structures in salivary glands. Mechanistically, the frequency of activated CD44high/CD62Llow CD4+ T cell populations was significantly decreased and this reduction was correlated with an increased number of CD44low/CD62Lhigh resting T cells. The CD8 T cell compartment was not affected. P140 down-regulated the maturation and differentiation of B cells into plasma cells, and decreased IgG and autoantibody secretion. It had no effect on germinal centers B cells (B220+ FAS+GL-7+) that are an important compound of the B cell humoral immune response. Together with previous data generated in MRL/lpr mice that develop some features of Sjögren's syndrome associated to other inflammatory and autoimmune defects, our present findings strongly reinforce the potential of autophagy modulators, such as P140, for treating patients with Sjögren's syndrome.

译文

自噬的失调与包括自身免疫性疾病在内的各种疾病适应症的发展有关。在这里,我们确定了迄今为止在 NOD 唾液腺和脾脏发生的大自噬途径的早期阶段发生的未知的自噬分子改变。H-2h4 老鼠,发展成一种原发性 sj ö gren's 样综合征。在本研究中,我们研究了磷酸肽 P140 纠正 NOD.H-2h4 小鼠免疫改变的能力,以及对唾液腺三级淋巴结构新生的影响,这是 SS 的特征。磷酸肽 P140 已知能降低过度的自噬过程,拯救生病的 NOD。H-2h4 小鼠一些自噬缺陷,并显著减少唾液腺三级淋巴结构的形成。从机制上来说,活化的 CD44high/CD62Llow CD4 T 细胞群体的频率显著降低,并且这种降低与 CD44low/CD62Lhigh 静息 T 细胞数量的增加相关。CD8 T 细胞室不受影响。P140 下调 b细胞向浆细胞的成熟和分化,降低 IgG 和自身抗体分泌。它对作为 b细胞体液免疫反应重要化合物的生发中心 b细胞 (B220 FAS GL-7) 没有影响。连同先前在 MRL/lpr 小鼠中产生的数据,这些小鼠发展了与其他炎症和自身免疫缺陷相关的干燥综合征的一些特征,我们目前的发现强烈加强了自噬调节剂的潜力, 如 P140,用于治疗干燥综合征患者。

Autophagy

儿科 应激过程 临床研究术语
概述  :  

细胞自噬作为真核细胞内一种应激过程,涉及细胞内众多信号途径及生物大分子以及受损细胞器的降解、循环。自噬过程中,细胞利用溶酶体内的水解酶将细胞质内受损的亚细胞器、非正确折叠的蛋白质等物质降解为脂肪酸、氨基酸等物质,并将这些物质循环再利用,维持细胞内物质与能量的稳定,使细胞在不同生理状态下保持正常。LC3-II、Beclin-1和P62均是自噬的标志性蛋白。过程 A:细胞接受自噬诱导信号后,在胞浆的某处形成一个小的类似“脂质体”样的膜结构,然后不断扩张,但它并不呈球形,而是扁平的,就

autophagy 英 /ɔː'tɒfədʒɪ/  美 /ɔ'tɑfədʒi/

释    义   n. 自我吞噬;自食症;自体吞噬

例    句   Autophagy appears to involve an active participation of the vacuolar membranes . 自体吞噬似乎与液泡膜的积极参加有关。

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