Macrophages are dominant innate immune cells. They demonstrate remarkable heterogeneity and plasticity that are essential for homeostasis and host defense. The heterogeneity of tissue macrophages is shaped by the ontogeny

tissue factors

and environmental signals

a pattern in a tissue-associated latitudinal manner. At the same time

macrophages have long been considered as mainly plastic cells. These cells respond to stimulation quickly and in a stimulus-specific way by utilizing a longitudinal cascaded activation

including coordination of signal transducer

epigenetic elements

and transcription factors

conclusively determine the macrophage phenotypes and functions. With the development of cutting-edge technologies

such as fate-mapping

single-cell transcriptomics

ipsc platform

nanotherapeutic materials

etc.

our understanding of macrophage biology and the roles in the pathogenesis of diseases is much advanced. This review summarizes recent progress on the latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases. The latitudinal regulation covers the tissue macrophage origins

tissue factors

and environmental signals

reflecting the macrophage heterogeneity. The longitudinal regulation focuses on how multiple factors shape the phenotypes and functions of macrophage subsets to gain plasticity in inflammatory diseases (i.e.

inflammatory bowel disease). In addition

how to target macrophages as a potential therapeutic approach and cutting edge-technologies for tissue macrophage study are also discussed in this review.