Macrophages are key cells of innate immunity that play an important role in regulating the inflammatory response, tissue repair processes, and the development of various pathological conditions, in particular, cancer and chronic inflammatory diseases. The functional activity of macrophages is largely determined by microenvironment signals, including cytokines, hormones, growth factors, and pathogen-associated molecular structures. The purpose of the study was to summarise contemporary scientific data on the molecular mechanisms of regulation of functional activity of macrophages under the influence of microenvironment factors and analyse the interaction of signalling pathways that determine their polarisation and functional plasticity. The paper analysed the results of contemporary studies on the regulation of macrophage signalling cascades involving Th1- and Th2-type cytokines, glucocorticoids, transforming growth factor β (TGF-β), and signalling pathways activated by pathogen-associated molecular structures. Activation of receptor complexes, in particular TLR4, has been shown to trigger complex signalling cascades associated with activation of the transcription factor NF-κB and MyD88-dependent signal transmission mechanisms. It was found that the interaction of various signalling molecules can lead to both synergistic and antagonistic effects affecting the expression of genes associated with the inflammatory response, cell adhesion, and lipid metabolism. The generalised data obtained confirmed the concept of a continuum of functional states of macrophages, according to which these cells are able to change their phenotype depending on the conditions of the microenvironment. These results highlighted the importance of investigating the mechanisms of interaction between different microenvironment signals to understand the regulation of macrophage functions. The practical significance of the study lies in the systematisation of recent ideas about the mechanisms of macrophage regulation, which can be used for further research on the molecular basis of the immune response, and for the development of new approaches to the treatment of inflammatory, autoimmune and oncological diseases
Anhelina Andriushchenko (Tue,) studied this question.