Embigin Function and Regulation in Human and Murine Macrophages

Abstract

Macrophages are the innate immune cells of the body, functioning as part of the physiological defence mechanism, as well as a finely tuned tissue repair system. Macrophages are categorized into two major classes of pro-inflammatory “M1” and anti-inflammatory “M2” macrophages, with tumor-associated macrophages being part of this class, where the pro-inflammatory cells drive defence responses while the anti-inflammatory macrophages mediate tissue repair and wound healing. This study aims to study the expression profile and potential functional roles of embigin, a membrane glycoprotein that has been associated with cell adhesion as well as developmental roles, in different macrophage populations from both mouse and human origins. Although embigin has been studied in other tissue types, its functions in macrophages remain unclear. This study utilizes a multi-method approach to identify the expression patterns and suggest potential functions for embigin in macrophages by analyzing multiple samples at the three biochemical landscapes of transcript, protein, and metabolite. The findings suggest that embigin is differentially expressed in macrophage subtypes, where the M2-like macrophages upregulate embigin transcripts as well as the embigin protein, demonstrated by the M2a subtype exhibiting the highest amount of embigin protein among the other M2-like phenotypes. Notably, the M2a phenotype is known to be the extreme end of anti-inflammatory activity, which underlines the correlation between embigin expression and anti-inflammatory polarization. Embigin is known to associate with monocarboxylate transporters (MCTs) as an ancillary protein facilitating their trafficking and function. This study finds different MCTs to be differentially expressed as well, with MCT1, mainly a lactate importer, being upregulated in M2-like macrophages, whereas MCT4, a lactate exporter, is downregulated, which indicates a change in the metabolic state of macrophages to favor lactate uptake. SMOC1, a protein previously shown to modulate phagocytic activity in macrophages, is upregulated in embigin knockout mice. Together, these results contribute to the further understanding of the roles of embigin in macrophages and provide potential future trajectories for immunology research focusing on embigin.