Abstract
Macrophages, important cells of innate immunity, are known for their phagocytic activity, capability for antigen presentation, and flexible phenotypes. Macrophages are found in all tissues and therefore represent an attractive therapeutic target for the treatment of diseases of various etiology. Genetic programming of macrophages is an important issue of modern molecular and cellular medicine. The controllable activation of macrophages towards desirable phenotypes in vivo and in vitro will provide effective treatments for a number of inflammatory and proliferative diseases. This review is focused on the methods for specific alteration of gene expression in macrophages, including the controllable promotion of the desired M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes in certain pathologies or model systems. Here we review the strategies of target selection, the methods of vector delivery, and the gene editing approaches used for modification of macrophages.
Highlights
Demonstrates that in the histone deacetylase 9 knockout mice (Hdac9-/- ), macrophages are inclined towards M2 phenotypes and show decreased expression of the pro-inflammatory M1 markers [31]
Relevance of these cells as therapeutics certainly depends on the possibility of correcting their transcriptome, optionally by genome editing, and reprogramming them in order to restore or activate certain functions involved in stimulating tissue regeneration or anti-tumor activity
Each article cited in this review highlights the specificity and uniqueness of the effects for a particular method; put together, these works demonstrate the striking versatility of the use of innate immunity cells in studying and treatment of various diseases
Summary
Discovered at the end of 19th century by Ilya Mechnikov [1], macrophages have been identified in all tissues Their chief competences are phagocytic activity and antigen presentation. The first generation develops from the extraembryonic yolk sac posterior plate mesoderm in the blood islands [7,8] These cells apparently give rise to the microglia of the central nervous system [9]. Activation of macrophages towards M2 phenotypes can be induced by antigen-antibody complexes, invading helminths, complement system components, apoptotic cells, interleukins (IL-4, IL-13, and IL-10), and transforming growth factor beta (TGF-β). Activation with these inducers drives macrophages towards the increased secretion of IL-10 and reduced secretion of IL-12 typical of the. IL-4, IL-13, IL-10, IL-33, TGF-β search for the genes encoding proteins that regulate (activate or repress) the expression of effector molecules
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