Röszer Tamás
Institute of Comparative Molecular Endocrinology, University of Ulm, Science Park I, Helmholtzstrasse 8/1, 89081, Ulm, Germany.
Apoptosis. 2017 Feb;22(2):284-294. doi: 10.1007/s10495-016-1310-x.
Apoptotic cell clearance by macrophages is key for normal tissue development and homeostasis. Nuclear receptors, such as peroxisome proliferator activated receptors (PPARs), liver X receptor (LXR), retinoic acid receptor (RAR), retinoid X receptor (RXR) and glucocorticoid receptor (GR) orchestrate this vital process. The underlying mechanism involves the transcriptional control of key genes of apoptotic cell recognition and internalization, such as Cd36, Mertk, Axl, C1qa, Tgm2, Abca1. In addition, apoptotic cell uptake leads to M2 activation of macrophages, and this process is also controlled at the gene transcription level by nuclear receptors. Apoptotic cells provide signals for nuclear receptors, which in turn accelerate the safe disposal of apoptotic debris, which eventually allows renewal of the tissues, and impedes the development of inflammation and autoimmunity against dying cells. Nuclear receptor signaling is vulnerable to endocrine disruptors, which may interfere with the ability of macrophages to phagocytose and acquire M2 activation. This review summarizes the mechanisms, which allow nuclear receptors to control apoptotic cell clearance by macrophages.
巨噬细胞对凋亡细胞的清除是正常组织发育和体内平衡的关键。核受体，如过氧化物酶体增殖物激活受体（PPARs）、肝X受体（LXR）、视黄酸受体（RAR）、视黄醇X受体（RXR）和糖皮质激素受体（GR）协调这一重要过程。其潜在机制涉及对凋亡细胞识别和内化的关键基因的转录控制，如Cd36、Mertk、Axl、C1qa、Tgm2、Abca1。此外，凋亡细胞的摄取导致巨噬细胞的M2活化，这一过程在基因转录水平上也受核受体控制。凋亡细胞为核受体提供信号，反过来加速凋亡碎片的安全清除，最终实现组织更新，并抑制针对垂死细胞的炎症和自身免疫的发展。核受体信号易受内分泌干扰物影响，内分泌干扰物可能干扰巨噬细胞吞噬和获得M2活化的能力。本综述总结了核受体控制巨噬细胞清除凋亡细胞的机制。
