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

Read more

Summary

Development of Macrophages

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

Macrophages as Perfect Cells for Reprogramming
The M1 Macrophage Applications
The M2 Macrophage Applications
Inflammatory Diseases
Proliferative Diseases
Early Attempts at Obtaining Specific Phenotypes
Activation with Signaling Molecules
Identification of Relevant Genomic Targets
Transient Modifications
Genome Editing
Delivery of Genetic Constructs to Cells
The Induced Pluripotent Stem Cell Technologies
In Vivo Models for Genome Editing
Conclusions
Results
Methods

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.