Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Bryan Heit

Abstract

Efferocytosis is the clearance of apoptotic cells and is necessary for homeostasis. Mer Tyrosine Kinase (MerTK) is a crucial efferocytic receptor whose loss is associated with chronic inflammatory diseases and autoimmunity. While previous studies have shown that MerTK mediates efferocytosis through a unique mechanism that requires integrins, MerTK signalling pathway remains unknown. Given this unusual internalization mechanism, I hypothesized that MerTK signals and engages integrins through a novel signalling pathway different from that used by other phagocytic receptors. Therefore, this study aimed to identify the signalling pathways activated by MerTK, utilizing conventional cell biology and pharmacological approaches.

I found that M0 and M2, but not M1 primary human macrophages, expressed MerTK. Moreover, crosslinking MerTK induced endocytosis in a MerTK-dependent manner, which was independent of the common regulators of phagocytosis. Furthermore, crosslinking MerTK resulted in intracellular tyrosine phosphorylation partially dependent on Syk/Src-family kinases and PI3-kinase, which denote their importance in MerTK tyrosine phosphorylation.


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