摘要
“自杀emperipolesis”是一个最近报道过程导致cell-in-cell结构,促进细胞死亡。这个过程是在研究调查发现autoreactive CD8 T细胞激活的命运在肝脏。最近,我们报道,激活T细胞侵入肝细胞,形成瞬态cell-in-cell结构,并迅速在endosomal /溶酶体隔间non-apoptotic通路中退化。重要的是,药物抑制这一过程引起肝内积累组织反应 T细胞和免疫耐受。描述emperipolesis的自杀分子机制仍处于起步阶段,但初步研究显示这种现象是不同于其他报道cell-in-cell结构。相对于其他cell-in-cell结构的形成,自杀emperipolesis发生在一个良性的环境中,没有明显的病理。这是为什么,在高等生物中,cell-in-cell结构在正常生理作用维持体内平衡。在人类各种慢性肝脏疾病,肝细胞内T细胞emperipolesis也被病理学家观察到。在正常生理机能时,T cell-in-hepatocyte结构造成自杀emperipolesis被短暂的观察到,在肝脏疾病严重的组织损伤,emperipolesis积累,者按时组织的损伤是由,或与有缺陷的T细胞间隙有关。在本文中,我们比较“自杀emperipolesis”其他进程导致cell-in-cell结构,并考虑其潜在维持免疫内稳态和在肝的环境中的生物角色。
关键词: Autoimmunity
Current Molecular Medicine
Title:Suicidal emperipolesis: a process leading to cell-in-cell structures, T cell clearance and immune homeostasis.
Volume: 15 Issue: 9
Author(s): F. Sierro, S. S. Tay, A. Warren, D. G. Le Couteur, G. W. McCaughan, D. G. Bowen and P. Bertolino
Affiliation:
关键词: Autoimmunity
摘要: “Suicidal emperipolesis” is one of the most recently reported processes leading to cell-in-cell structures that promote cell death. This process was discovered in studies investigating the fate of autoreactive CD8 T cells activated within the liver. Recently, we reported that activated T cells invaded hepatocytes, formed transient cell-in-cell structures, and were rapidly degraded within endosomal/lysosomal compartments by a non-apoptotic pathway. Importantly, pharmacological inhibition of this process caused intrahepatic accumulation of tissue-reactive T cells and breach of immune tolerance. The characterization of the molecular mechanisms of suicidal emperipolesis is still in its infancy, but initial studies suggest this phenomenon is distinct from other reported cell-in-cell structures. As opposed to the formation of other cell-in-cell structures, suicidal emperipolesis takes place in a non-malignant environment, and without obvious pathology. It is therefore the first cell-in-cell structure described to have a role in maintaining homeostasis in normal physiology in higher organisms. T cell emperipolesis within hepatocytes has also been observed by pathologists in a range of chronic human liver pathologies. As T cell-in-hepatocyte structures resulting from suicidal emperipolesis are very transiently observed in normal physiology, their accumulation during liver disease would suggest that severe tissue injury is promoted by, or associated with, defective T cell clearance. In this review, we compare “suicidal emperipolesis” to other processes leading to cell-in-cell structures, and consider its potential biological roles in maintaining immune homeostasis and tolerance in the context of the hepatic environment.
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Cite this article as:
F. Sierro, S. S. Tay, A. Warren, D. G. Le Couteur, G. W. McCaughan, D. G. Bowen and P. Bertolino , Suicidal emperipolesis: a process leading to cell-in-cell structures, T cell clearance and immune homeostasis., Current Molecular Medicine 2015; 15 (9) . https://dx.doi.org/10.2174/1566524015666151026102143
DOI https://dx.doi.org/10.2174/1566524015666151026102143 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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