Macroautophagy is deregulated in murine and human lupus T lymphocytes.
Macroautophagy is deregulated in murine and human lupus T lymphocytes.
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DOI：
10.4161/auto.20275
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发表时间：
2012-07-01
期刊：
影响因子：
13.3
通讯作者：
Muller S
中科院分区：
文献类型：
--
作者：
Gros F;Arnold J;Page N;Décossas M;Korganow AS;Martin T;Muller S
最近研究表明，巨噬细胞既能调节淋巴细胞生物学，又能调节天然免疫。在这项研究中，我们试图确定自噬的解除管制是否与自身免疫的发展有关。全基因组关联研究已经指出了与系统性红斑狼疮相关的核苷酸多态，但自噬在系统性红斑狼疮发病和/或发展中的潜在作用尚不清楚。在这里，我们提供了狼疮大范围自噬放松调控的第一个线索。通过LC3转换实验和电子显微镜实验，我们观察到两种不同的狼疮易感小鼠模型MRLlpr/LPR和(NZB/NZW)F1的T细胞与非病理对照CBA/J和BALB/c小鼠相比，具有较高的自噬能力。与正常小鼠不同，小鼠狼疮的自噬随着年龄的增长而增加。在体内，CBA/J对照组小鼠的脂多糖刺激有效地激活了T淋巴细胞，但不能上调这些细胞中自噬间隔的形成。这反对完全由急性炎症损伤引起的狼疮T细胞自噬的解除管制。经电子显微镜定量的自噬空泡在狼疮患者的T细胞中的频率也明显高于健康对照组和非狼疮自身免疫性疾病患者。这种自噬结构数量的增加并不是均匀分布的，在某些T细胞中似乎更明显。这些结果表明，自噬可以调节狼疮过程中自身反应性T细胞的存活，从而可能导致设计新的狼疮治疗方案。
Macroautophagy was recently shown to regulate both lymphocyte biology and innate immunity. In this study we sought to determine whether a deregulation of autophagy was linked to the development of autoimmunity. Genome-wide association studies have pointed out nucleotide polymorphisms that can be associated with systemic lupus erythematosus, but the potential role of autophagy in the initiation and/or development of this syndrome is still unknown. Here, we provide first clues of macroautophagy deregulation in lupus. By the use of LC3 conversion assays and electron microscopy experiments, we observed that T cells from two distinct lupus-prone mouse models, i.e., MRLlpr/lpr and (NZB/NZW)F1, exhibit high loads of autophagic compartments compared with nonpathologic control CBA/J and BALB/c mice. Unlike normal mice, autophagy increases with age in murine lupus. In vivo lipopolysaccharide stimulation in CBA/J control mice efficiently activates T lymphocytes but fails to upregulate formation of autophagic compartments in these cells. This argues against a deregulation of autophagy in lupus T cells solely resulting from an acute inflammation injury. Autophagic vacuoles quantified by electron microscopy are also found to be significantly more frequent in T cells from lupus patients compared with healthy controls and patients with non-lupus autoimmune diseases. This elevated number of autophagic structures is not distributed homogeneously and appears to be more pronounced in certain T cells. These results suggest that autophagy could regulate the survival of autoreactive T cell during lupus, and could thus lead to design new therapeutic options for lupus.
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DOI：
10.1084/jem.20061303
发表时间：
2007-01-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pua HH;Dzhagalov I;Chuck M;Mizushima N;He YW
通讯作者：
He YW
免疫相关的GTPase IRGM1通过防止干扰素γ诱导的细胞死亡促进活化的CD4+ T细胞群体的扩张。
影响因子：
30.5
作者：
Feng, Carl G.;Zheng, Lixin;Jankovic, Dragana;Bafica, Andre;Cannons, Jennifer L.;Watford, Wendy T.;Chaussabel, Damien;Hieny, Sara;Caspar, Patricia;Schwartzberg, Pamela L.;Lenardo, Michael J.;Sher, Alan
通讯作者：
Sher, Alan
影响因子：
15.9
作者：
Espert, Lucile;Denizot, Melanie;Biard-Piechaczyk, Martine
通讯作者：
Biard-Piechaczyk, Martine
影响因子：
27.4
作者：
Page, Nicolas;Gros, Frederic;Muller, Sylviane
通讯作者：
Muller, Sylviane
影响因子：
7.5
作者：
Yang Z;Klionsky DJ
通讯作者：
Klionsky DJ