Transcriptional control of apoptotic cell clearance by macrophage nuclear receptors.

ABSTRACT

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.