LC3-Associated Phagocytosis and Inflammation.
LC3-Associated Phagocytosis and Inflammation.
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DOI：
10.1016/j.jmb.2017.08.012
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发表时间：
2017-11-24
影响因子：
5.6
通讯作者：
Green DR
中科院分区：
文献类型：
--
作者：
Heckmann BL;Boada-Romero E;Cunha LD;Magne J;Green DR
LC3相关吞噬（LAP）是一种新型的非典型自噬形式，其中LC3（微管相关蛋白1A/ 1b -轻链3）利用一部分典型自噬机制结合到吞噬体膜上。LAP对免疫调节的影响在专业吞噬细胞，特别是巨噬细胞中得到了最好的表征，其中LAP在清除细胞外颗粒（包括凋亡细胞和病原体）方面发挥了重要作用。通过巨噬细胞表面的受体与死细胞的结合导致自噬机制向吞噬体的易位，最终导致LC3结合。这些事件促进了一种快速的吞噬作用，对凋亡细胞产生“免疫沉默”的清除。LAP缺乏的后果包括清除死亡细胞的能力下降和小鼠狼疮样自身免疫性疾病的建立。LAP减轻自身免疫的能力可能是通过抑制吞噬死亡细胞时的促炎信号和防止自身抗原向其他免疫细胞递呈而发生的。然而，目前尚不清楚LAP如何在分子水平上影响免疫反应的激活和结果。在此，我们对LAP及其在免疫应答中的已知作用进行了详细的回顾，并对LAP可能通过巨噬细胞的代谢重编程和极化调节免疫功能的推测机制进行了进一步的推测。
LC3-associated phagocytosis (LAP) is a novel form of non-canonical autophagy where LC3 (microtubule-associated protein 1A/1B-light chain 3) is conjugated to phagosome membranes using a portion of the canonical autophagy machinery. The impact of LAP to immune regulation is best characterized in professional phagocytes, in particular macrophages, where LAP has instrumental roles in the clearance of extracellular particles including apoptotic cells and pathogens. Binding of dead cells via receptors present on the macrophage surface results in the translocation of the autophagy machinery to the phagosome and ultimately LC3 conjugation. These events promote a rapid form of phagocytosis that produces an “immunologically silent” clearance of the apoptotic cells. Consequences of LAP deficiency include a decreased capacity to clear dying cells and the establishment of a lupus-like autoimmune disease in mice. The ability of LAP to attenuate autoimmunity likely occurs through the dampening of pro-inflammatory signals upon engulfment of dying cells and prevention of autoantigen presentation to other immune cells. However, it remains unclear how LAP shapes both the activation and outcome of the immune response at the molecular level. Herein, we provide a detailed review of LAP and its known roles in the immune response and provide further speculation on the putative mechanisms by which LAP may regulate immune function, perhaps through the metabolic reprogramming and polarization of macrophages.
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DOI：
10.1126/science.1227026
发表时间：
2012-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Choy A;Dancourt J;Mugo B;O'Connor TJ;Isberg RR;Melia TJ;Roy CR
通讯作者：
Roy CR
选择性自噬：异种。
影响因子：
4.8
作者：
Bauckman, Kyle A.;Owusu-Boaitey, Nana;Mysorekar, Indira U.
通讯作者：
Mysorekar, Indira U.
影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
13.3
作者：
Cemma, Marija;Grinstein, Sergio;Brumell, John H.
通讯作者：
Brumell, John H.
影响因子：
20.1
作者：
Bentzon, Jacob Fog;Otsuka, Fumiyuki;Falk, Erling
通讯作者：
Falk, Erling