Autophagy and Autophagy-Related Proteins in CNS Autoimmunity.
Autophagy and Autophagy-Related Proteins in CNS Autoimmunity.
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DOI：
10.3389/fimmu.2017.00165
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发表时间：
2017
影响因子：
7.3
通讯作者：
Lünemann JD
中科院分区：
文献类型：
--
作者：
Keller CW;Lünemann JD
自噬包括一组异质性的细胞途径，使真核细胞能够将细胞质成分传递给溶酶体降解，回收营养物质，并在饥饿期间存活。除了这些原始功能外，自噬已成为协调先天和适应性免疫反应的关键机制，并通过向主要组织相容性复合体（MHC） ii类含室（MIICs）递送肽来形成CD4+ T细胞免疫。单独的自噬蛋白还可以调节MHC I类分子的表达，从而激活CD8+ T细胞。自身反应性CD4+和CD8+ T细胞的出现和扩增被认为在多发性硬化症（MS）及其动物模型实验性自身免疫性脑脊髓炎的发病机制中起关键作用。支持T淋巴细胞存活和增殖的必需自噬相关蛋白5 （Atg5）的表达在从复发缓解型多发性硬化症患者的血液或脑组织中分离的T细胞中增加。Atg5是否通过自噬介导的抗原递呈促进自身反应性T细胞的激活尚不完全清楚。在这里，我们讨论自噬蛋白和途径在调节T细胞免疫中的复杂功能及其在MS发生和进展中的潜在作用。
Autophagy comprises a heterogeneous group of cellular pathways that enables eukaryotic cells to deliver cytoplasmic constituents for lysosomal degradation, to recycle nutrients, and to survive during starvation. In addition to these primordial functions, autophagy has emerged as a key mechanism in orchestrating innate and adaptive immune responses and to shape CD4+ T cell immunity through delivery of peptides to major histocompatibility complex (MHC) class II-containing compartments (MIICs). Individual autophagy proteins additionally modulate expression of MHC class I molecules for CD8+ T cell activation. The emergence and expansion of autoreactive CD4+ and CD8+ T cells are considered to play a key role in the pathogenesis of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis. Expression of the essential autophagy-related protein 5 (Atg5), which supports T lymphocyte survival and proliferation, is increased in T cells isolated from blood or brain tissues from patients with relapsing-remitting MS. Whether Atgs contribute to the activation of autoreactive T cells through autophagy-mediated antigen presentation is incompletely understood. Here, we discuss the complex functions of autophagy proteins and pathways in regulating T cell immunity and its potential role in the development and progression of MS.