Macrophage Epigenetic Regulation and Organ Transplantation

As research has progressed, immunologists and transplantation scientists have gradually appreciated that macrophages hold a pivotal role in the immunopathology of organ transplantation, with more and more great efforts being devoted to them. Due to their heterogeneity and plasticity, macrophages play diverse and highly intricate roles in allografts. Their effects on various biological process regulation and immunogenicity aspects of transplant outcomes have been shown to correlate with functional evidence of organ transplantation pathophysiology and its potential therapeutic implications, ranging from the initial immune response to the long-term response.

The long-term significant role of macrophages in immune surveillance and maintenance of homeostasis in transplanted organs can be explained by epigenetic modifications involving long-term functional reprogramming of bone marrow cells, including non-coding RNA and covalent modifications of DNA and histones. Histone modifications are the most prevalent (including acetylation, methylation, phosphorylation, ubiquitination, crotonylation, and polymerization, with undescribed modifications still emerging). However, the functional contribution of epigenetics to the immunopathology of organ transplant macrophages has not been thoroughly investigated, and recent advances have placed macrophages at the forefront of epigenetic and transplantation research.

The purpose of this Research Topic is to provide a forum for further research into the role of macrophages in the pathogenesis and development of immunopathology in transplantation, with a focus on epigenetic functional evidence of histone epigenetic modification involved in the pathogenesis of organ transplant pathology and its potential therapeutic implications. In addition, we aim to elucidate and enrich the post-translational regulatory mechanism, paving the way for the exploration of the pathological study of organ transplantation. Ultimately, the goal is to explore innovative epigenetic targeted pharmacological interventions and the potential for prevention, to provide the scientific basis for a favorable outcome in clinical diagnosis and treatment.

Subtopics of interest include but are not limited to:
1) Heterogeneity, diversity, and plasticity of macrophages in organ transplantation, including tissue-specific macrophages;
2) Divergent epigenetic alterations of macrophages in organ transplantation pathophysiology;
3) Multiple post-translational modifications (PTM) and signaling cascades of macrophage involvement in organ transplantation, including training-mediated immune pathways;
4) Evidence for an alloantigen-specific memory response of macrophages and their epigenetic modifications;
5) Crosstalk of epigenetic modification networks with each other in the surrounding related proteins of macrophages;
6) Related inhibitors of chromatin modifying enzymes and their therapeutic potential;
7) Human and/or veterinary clinical trials using chromatin-modifying enzyme inhibitors against various transplantation complications;
8) Combination studies – e.g. PTM inhibitors + related pathway inhibitors;
9) Use of quantitative proteomics and other emerging tools to systematically study PTM-driven protein stability regulation;
10) The prospects and implications for the development of future clinical therapeutics.


Posted on

November 30, 2017