Phagocytic phosphatidylserine receptors (PSRs)

Phagocytic phosphatidylserine receptors are a diverse group of cell surface proteins expressed on macrophages, dendritic cells, and other phagocytes that specifically recognize phosphatidylserine (PS) exposed on the outer leaflet of apoptotic cell membranes (Birge et al., 2016, Nature Reviews Immunology). Under normal physiological conditions, the interaction between PS and these receptors triggers efferocytosis, a process of silent, non-inflammatory clearance of dying cells that is crucial for tissue homeostasis and the resolution of inflammation (Lemke, 2013, Cold Spring Harbor Perspectives in Biology). This class includes direct receptors like TIM-4, BAI1, and Stabilin-2, as well as indirect receptors like the TAM family (Tyro3, Axl, and MerTK) which utilize bridging molecules such as Gas6 or Protein S to bind PS (UniProt P51813, O00519, Q06418). In the context of the tumor microenvironment, many cancers exploit these pathways to promote an immunosuppressive environment, thereby evading immune detection. Consequently, therapeutic strategies targeting these receptors, particularly the TAM family, are being developed to restore anti-tumor immunity and enhance the efficacy of existing immunotherapies (Graham et al., 2014, Nature Reviews Cancer).

Other names

Phosphatidylserine receptorsPS receptorsEfferocytosis receptorsApoptotic cell clearance receptorsTAM receptorsTIM receptors

Modulation of efferocytosis and immune signaling through the inhibition or activation of receptors that recognize phosphatidylserine, either directly or via bridging molecules, to alter the inflammatory state of the microenvironment.