Factors regulating microglia activation

Abstract

Microglia are resident macrophages of the central nervous system (CNS) that display high functional similarities to other tissue macrophages. However, it is especially important to create and maintain an intact tissue homeostasis to support the neuronal cells, which are very sensitive even to minor changes in their environment. The transition from the "resting" but surveying microglial phenotype to an activated stage is tightly regulated by several intrinsic (e.g., Runx-1, Irf8, and Pu.1) and extrinsic factors (e.g., CD200, CX3CR1, and TREM2). Under physiological conditions, minor changes of those factors are sufficient to cause fatal dysregulation of microglial cell homeostasis and result in severe CNS pathologies. In this review, we discuss recent achievements that gave new insights into mechanisms that ensure microglia quiescence.

Keywords: activation; development; microglia; silencing; transcription factors.

FIGURE 1

Exogenous signals and their receptors on microglia. Microglia are equipped with a group of surface receptors which trigger signals in microglia under “resting” conditions. Many of these signals are ligands which are released or expressed on the surface of neurons. Inhibitory receptors like CX₃CR1, CD200R, and CD172a/Sirp alpha have their ligands on the surface of healthy neurons. A loss of the signal also indicates a loss of neuronal integrity. Receptors such as TREM2 and purinergic receptors are essential to mimic neuronal injury and induce phagocytotic and anti-inflammatory functions in microglia. The crosstalk between microglia and neurons is also important for the survival of microglia. Neurons release factors like IL-34 and Csf1 which bind to Csf1r on the surface of microglia and induce cell survival or proliferation.