2016年10月10日，國(guó)際學(xué)術(shù)權(quán)威刊物自然出版集團(tuán)旗下子刊《Nature Reviews Immunology》雜志在線發(fā)表了中國(guó)科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所許琛琦研究員題為“Regulation of T cell signaling by membrane lipids”的科研綜述，該論文綜述了細(xì)胞膜脂質(zhì)分子對(duì)T淋巴細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)的調(diào)控機(jī)制以及基于脂質(zhì)分子的免疫治療方法。
細(xì)胞膜是一種將細(xì)胞內(nèi)容物與細(xì)胞外環(huán)境隔離的重要細(xì)胞結(jié)構(gòu)，同時(shí)細(xì)胞膜也負(fù)責(zé)細(xì)胞與環(huán)境的信息、物質(zhì)與能量的交換，為細(xì)胞維持正常的生理狀態(tài)和發(fā)揮相應(yīng)的生理功能提供了重要的基礎(chǔ)。細(xì)胞膜上的脂質(zhì)分子種類復(fù)雜繁多，隨著近些年來(lái)脂質(zhì)組學(xué)和成像技術(shù)的發(fā)展，我們對(duì)于細(xì)胞膜上脂質(zhì)分子動(dòng)態(tài)性的理解在不斷地加深。細(xì)胞膜上的脂質(zhì)分子可以通過(guò)多種方式調(diào)控T淋巴細(xì)胞的信號(hào)傳導(dǎo)，并且一種脂質(zhì)分子往往有多種調(diào)控功能。值得一提的是，近期研究表明可以通過(guò)調(diào)節(jié)細(xì)胞膜上的脂質(zhì)分子含量來(lái)改變T淋巴細(xì)胞的活性狀態(tài)從而治療腫瘤和自身免疫疾病，代表了一種新的治療思路。
許琛琦研究員長(zhǎng)期致力于T淋巴細(xì)胞與疾病的研究。前期研究發(fā)現(xiàn)酸性磷脂可以在靜息態(tài)的T淋巴細(xì)胞中屏蔽TCR的功能位點(diǎn)，從而保證細(xì)胞不會(huì)自動(dòng)活化(Cell，2008);而鈣離子可以在活化的T淋巴細(xì)胞中通過(guò)影響酸性磷脂的帶電性來(lái)解除TCR的屏蔽，從而放大了TCR的活化信號(hào)并由此提高T淋巴細(xì)胞對(duì)抗原的敏感性(Nature，2013)。另外通過(guò)合作研究發(fā)現(xiàn)酸性磷脂與鈣離子也能調(diào)控BCR的活化(Nature Communication，2015)。近期發(fā)現(xiàn)通過(guò)調(diào)節(jié)T淋巴細(xì)胞膽固醇代謝可以提高細(xì)胞膜膽固醇水平，從而促進(jìn)T淋巴細(xì)胞對(duì)腫瘤的殺傷，由此發(fā)展了一種新的腫瘤免疫治療方法(Nature，2016)。
原文鏈接：
Regulation of T cell signalling by membrane lipids
原文摘要：
The plasma membrane is an essential cellular structure that separates the cell interior from the extracellular environment, while allowing for the exchange of signals and materials that are essential for cell survival and function. The complexity of the lipids in the plasma membrane has been long appreciated, but recent developments in lipidomics and imaging technologies have improved our understanding of plasma membrane lipid dynamics. New studies have started to unveil important functions for plasma membrane lipids in regulating T cell signalling. importantly, it has been shown that the modulation of membrane lipids can be used to harness T cell activity to treat cancer and autoimmunity. Therefore, lipid-based immunotherapy might be a promising new clinical strategy.
