Macrophage polarization in sarcoidosis

Abstract

Sarcoidosis is a systemic inflammatory disease of unknown etiology, characterized by the formation of epithelioid cell granulomas, multisystem lesions with a certain frequency of involvement of various organs, mainly the lungs (up to 90% of cases). Over the past decade, significant progress has been made in understanding the pathogenesis of sarcoidosis, the important role of immunological, genetic and environmental factors in the development of this pathology has been established. It is believed that the leading mechanism in the pathogenesis of sarcoidosis is the aberrant activation of the innate and adaptive immune response to unidentified antigen(s), which leads to the development of granulomatous inflammation and the formation of granulomas. However, despite the huge number of studies that has been carried out, the mechanisms and signaling pathways that control the development of the inflammatory process during the formation of granulomas and the progression of pathology have not been fully determined.This literature review examines the important role of various cytokines and T helper subpopulations in sarcoidosis. Particular attention is paid to the cells of innate immunity – macrophages in the pathogenesis of this disease. These cells play a key role in the formation of sarcoid granulomas and in the pathogenesis of sarcoidosis. The macrophage population is characterized by plasticity and functional heterogeneity. In response to various signals from the microenvironment, macrophages are able to acquire certain phenotypes. The review considers the issues of polarization of macrophages, changes in the phenotype of these cells to subpopulations M1 (M1 phenotype; classically activated; pro-inflammatory) and M2 (M2 phenotype; alternatively activated, anti-inflammatory). These two cell populations are characterized by the expression of different markers on their surface, which allow these cells to differentiate from each other. The analysis of literature data on the levels of key polarizing cytokines for macrophages and cells-producers of these cytokines that patients with sarcoidosis have, in acute and chronic course of the disease, was carried out.Important aspects of the alternative activation of macrophages of the M2 phenotype and their division into subtypes: M2a, M2b, M2c, M2d are noted. The features of various subtypes’ activation of macrophages in this granulomatosis and their importance in the development and progression of pathology are considered. Studying the role of macrophages’ phenotypes, understanding the mechanisms by which the phenotypes of these cells are activated and modulated in various microenvironmental conditions, can contribute to the development and implementation into clinical practice of new therapeutic approaches for the treatment of sarcoidosis and many other forms of pathologies.