O death where is thy sting? Immunologic tolerance to apoptotic self.
O death where is thy sting? Immunologic tolerance to apoptotic self.
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DOI：
10.1007/s00018-013-1261-0
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发表时间：
2013-10
影响因子：
8
通讯作者：
McGaha, Tracy L.
中科院分区：
文献类型：
--
作者：
Ravishankar, Buvana;McGaha, Tracy L.
在高等生物体中，天生的清除细胞通过清除每天产生的数十亿个凋亡细胞来维持生理上的动态平衡。去除凋亡细胞需要专业和非专业吞噬细胞的有效识别和摄取，这些吞噬细胞由一系列可溶的和凋亡的细胞整合信号控制，导致免疫沉默的清除。虽然细胞凋亡与适应性和先天炎症免疫的深刻抑制有关，但在理解免疫耐受如何在分子或细胞水平上表现出来方面，我们才刚刚开始触及表面。在过去的10年中，有数据表明，专业吞噬细胞，尤其是基质巨噬细胞和CD8α+CD103+树突状细胞，在最终导致整个动物长期免疫耐受的调节级联反应的启动中起关键作用。重要的是，我们和其他实验室最近的工作表明，先天免疫系统对凋亡细胞的感知改变，要么是通过移除次级淋巴器官中的关键吞噬细胞哨兵，要么是通过阻断免疫抑制途径，导致明显的炎症，对自身的耐受性崩溃。这挑战了一种范式，即凋亡细胞天生具有免疫抑制作用，这表明凋亡细胞的耐受是一个“上下文相关”的事件。
In higher organisms, innate scavenging cells maintain physiologic homeostasis by removal of the billions of apoptotic cells generated on a daily basis. Apoptotic cell removal requires efficient recognition and uptake by professional and non-professional phagocytic cells, which are governed by an array of soluble and apoptotic cell-integral signals resulting in immunologically silent clearance. While apoptosis is associated with profound suppression of adaptive and innate inflammatory immunity, we have only begun to scratch the surface in understanding how immunologic tolerance to apoptotic self manifest at either the molecular or cellular level. In the last 10 years data has emerged implicating professional phagocytes, most notably stromal macrophages and CD8α+CD103+ dendritic cells, as critical in initiation of the regulatory cascade that will ultimately lead to long-term whole animal immune tolerance. Importantly, recent work by our lab and others has shown that alterations in apoptotic cell perception by the innate immune system either by removal of critical phagocytic sentinels in secondary lymphoid organs or blockage of immunosuppressive pathways leads to pronounced inflammation with a breakdown of tolerance towards self. This challenges the paradigm that apoptotic cells are inherently immunosuppressive suggesting that apoptotic cell tolerance is a “context dependent” event.
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影响因子：
56.9
作者：
Blander, JM;Medzhitov, R
通讯作者：
Medzhitov, R
影响因子：
37.8
作者：
Combadière, C;Potteaux, S;Mallat, Z
通讯作者：
Mallat, Z
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
3.9
作者：
Borisenko, GG;Matsura, T;Kagan, VE
通讯作者：
Kagan, VE
不变的天然杀手T细胞识别微生物危险信号引起的脂质自抗原。
影响因子：
30.5
作者：
Brennan, Patrick J.;Tatituri, Raju V. V.;Brigl, Manfred;Kim, Edy Y.;Tuli, Amit;Sanderson, Joseph P.;Gadola, Stephan D.;Hsu, Fong-Fu;Besra, Gurdyal S.;Brenner, Michael B.
通讯作者：
Brenner, Michael B.