Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Biochem Biophys Res Commun. 2013 Jan 11;430(2):689-94. doi: 10.1016/j.bbrc.2012.11.090. Epub 2012 Dec 2.
Autophagy contributes to the homeostasis of many tissues, yet its role in epithelia is incompletely understood. A recent report proposed that Atg5-dependent autophagy in thymic epithelial cells is essential for their function in the negative selection of self-reactive T-cells and, thus, for the suppression of tissue inflammation. Here we crossed mice carrying floxed alleles of the Atg5 gene with mice expressing the Cre recombinase under the control of the keratin K5 promoter to suppress autophagy in all K5-positive epithelia. The efficiency of autophagy abrogation was confirmed by immunoanalyses of LC3, which was converted to the autophagy-associated LC3-II form in normal but not Atg5-deficient cells, and of p62, which accumulated in Atg5-deficient cells. Mice carrying the epithelium-specific deletion of Atg5 showed normal weight gain, absence of tissue inflammation, and a normal morphology of the thymic epithelium. By contrast, autophagy-deficient epithelial cells of the preputial gland showed aberrant eosinophilic staining in histology and premature degradation of nuclear DNA during terminal differentiation. Taken together, the results of this study suggest that autophagy is dispensable for the suppression of autoimmunity by thymic epithelial cells but essential for normal differentiation of the preputial gland in mice.
自噬有助于许多组织的内稳态，但它在上皮细胞中的作用尚未完全了解。最近的一份报告提出，胸腺上皮细胞中依赖 Atg5 的自噬对于它们在自身反应性 T 细胞的阴性选择中的功能至关重要，从而抑制组织炎症。在这里，我们将 Atg5 基因的 floxed 等位基因的小鼠与在角蛋白 K5 启动子控制下表达 Cre 重组酶的小鼠进行杂交，以抑制所有 K5 阳性上皮细胞中的自噬。通过免疫分析 LC3 证实了自噬的阻断效率，LC3 在正常细胞中转化为自噬相关的 LC3-II 形式，但在 Atg5 缺陷细胞中没有转化，而 p62 在 Atg5 缺陷细胞中积累。携带上皮细胞特异性 Atg5 缺失的小鼠体重正常增加，组织炎症不存在，胸腺上皮细胞形态正常。相比之下，包皮腺的自噬缺陷上皮细胞在组织学上显示出异常的嗜酸性染色，并在终末分化过程中过早降解核 DNA。总之，这项研究的结果表明，自噬对于胸腺上皮细胞抑制自身免疫是可有可无的，但对于小鼠包皮腺的正常分化是必不可少的。
