Macrophage Polarization Group

Macrophages are very heterogenous and plastic cellular components of the innate immune system. They participate in the maintenance of normal tissue homeostasis, defense against different pathogen infections, regulation of inflammation, and tissue regeneration. Their functional properties are tightly determined by the molecular microenvironment, including various cytokines, pathogen-derived molecules, and lipids. The two available endpoints of macrophage polarization are the Th1-type cytokine IFNγ and Gram-negative bacterial cell wall-derived lipopolysaccharide-induced classical, and the Th2-type cytokines interleukin-4 and interleukin-13-induced alternative macrophage polarization. Classically polarized macrophages play an essential role in the defense against bacterial infections and inflammation. In contrast, the alternatively polarized macrophages participate in the tissue regeneration, development, and progression of allergic airway inflammation, asthma, fibrotic processes, and defense against nematode infections. However, in various pathological processes, many microenvironmental signals with opposing effects are present simultaneously or shifted in time, resulting in many different transitional macrophage polarization stages. These polarization forms can remarkably modulate disease development and progression.

The molecular microenvironment influences gene expression at various levels in macrophages, the most important is the regulation of the epigenetic and transcriptional program through the activation of signal-dependent transcription factors. Nevertheless, the complex interactions between epigenetic and transcriptional programs activated by different microenvironmental signals and the nature and molecular basis of transcriptional memory induced by individual signals are not fully understood. We aim to investigate the epigenetic bases and functional consequences of complex interactions between various microenvironmental signals and the transcriptional memory induced by macrophage polarization signals combining transcriptomic, epigenomic, and immunological approaches.