Delta- like ligand 4- expressing macrophages and human diseases: Insights into pathophysiology and therapeutic opportunities

Macrophages are key players in the immune response and have been implicated in various human diseases, including atherosclerosis, cancer, and chronic inflammatory disorders. While numerous studies have delved into the nuances of macrophage behavior in these conditions, there remains a gap in understanding the specific role of Delta-like ligand 4 (Dll4)-expressing macrophages and their overarching implications across these diseases. Among the plethora of factors expressed by macrophages, Dll4 has emerged as a molecule of particular interest. Recent studies have highlighted its unique role in modulating macrophage functions and its potential implications in various diseases. This review seeks to consolidate existing knowledge, address this gap, and present a comprehensive overview of Dll4-expressing macrophages in the context of these disorders and highlight their potential as therapeutic targets. We examined the involvement of Dll4-expressing macrophages in multiple human diseases such as atherosclerosis, cancer and chronic inflammatory diseases, emphasizing their influence on disease progression. We also discussed the challenges, limitations, and emerging research areas in targeting Dll4-expressing macrophages and provide an outlook on potential therapeutic strategies for the treatment of these diseases. By addressing the previously existing research gap, we've provided a roadmap that brings together fragmented insights, paving the way for more holistic research and potentially more effective therapeutic strategies centered on Dll4-expressing macrophages.