Occurrences and Functions of Ly6C(hi) and Ly6C(lo) Macrophages in Health and Disease

Macrophages originating from the yolk sac or bone marrow play essential roles in tissue homeostasis and disease. Bone marrow-derived monocytes differentiate into Ly6C(hi) and Ly6C(lo) macrophages according to the differential expression of the surface marker protein Ly6C. Ly6C(hi) and Ly6C(lo) cells possess diverse functions and transcriptional profiles and can accelerate the disease process or support tissue repair and reconstruction. In this review, we discuss the basic biology of Ly6C(hi) and Ly6C(lo) macrophages, including their origin, differentiation, and phenotypic switching, and the diverse functions of Ly6C(hi) and Ly6C(lo) macrophages in homeostasis and disease, including in injury, chronic inflammation, wound repair, autoimmune disease, and cancer. Furthermore, we clarify the differences between Ly6C(hi) and Ly6C(lo) macrophages and their connections with traditional M1 and M2 macrophages. We also summarize the limitations and perspectives for Ly6C(hi) and Ly6C(lo) macrophages. Overall, continued efforts to understand these cells may provide therapeutic approaches for disease treatment.