Macrophages are important players in the immune system that sense various tissue challenges and trigger inflammation. Tissue injuries are followed by inflammation, which is tightly coordinated with tissue repair processes. Dysregulation of these processes leads to chronic inflammation or tissue fibrosis. Wnt ligands are present both in homeostatic and pathological conditions. However, their roles and mechanisms regulating inflammation and tissue repair are being investigated. Here we aim to provide an overview of overarching themes regarding Wnt and macrophages by reviewing the previous literature. We aim to gain future insights into how tissue inflammation, repair, regeneration, and fibrosis events are regulated by macrophages.

Upon injury, inflammation and repair processes are orchestrated to maintain tissue homeostasis. The Wnt ligands play essential roles in cell differentiation and proliferation for tissue repair and regeneration. It is increasingly clear that Wnt ligands play crucial immune-modulatory roles in inflammatory diseases. It is predicted that comprehensive research regarding the cross-talk between nonimmune and immune cells in tissue injury and repair will flourish. The Wnt system and immune system interaction will be critical to understanding tissue injury, inflammation, and repair. In this study, we will first introduce the Wnt system and review the role of the Wnt system in tissue regeneration and repair. We will review the previous literature regarding how the Wnt ligands regulate the immune system. Next, we will discuss the current and future perspectives of Wnt ligands to target cancer and other immunological diseases. Finally, we will discuss the quintessential Wnt antagonist Dickkopf1 as an immunomodulatory ligand.