Abstract
Regulatory T cells (Tregs) are important mediators of immunological self-tolerance and homeostasis. Being cluster of differentiation 4+Forkhead box protein3+ (CD4+FOXP3+), these cells are a subset of CD4+ T lymphocytes and can originate from the thymus (tTregs) or from the periphery (pTregs). The malfunction of CD4+ Tregs is associated with autoimmune responses such as rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1D), inflammatory bowel diseases (IBD), psoriasis, systemic lupus erythematosus (SLE), and transplant rejection. Recent evidence supports an opposed role in sepsis. Therefore, maintaining functional Tregs is considered as a therapy regimen to prevent autoimmunity and allograft rejection, whereas blocking Treg differentiation might be favorable in sepsis patients. It has been shown that Tregs can be generated from conventional naïve T cells, called iTregs, due to their induced differentiation. Moreover, Tregs can be effectively expanded in vitro based on blood-derived tTregs. Taking into consideration that the suppressive role of Tregs has been mainly attributed to the expression and function of the transcription factor Foxp3, modulating its expression and binding to the promoter regions of target genes by altering the chromatin histone acetylation state may turn out beneficial. Hence, we discuss the role of histone deacetylation inhibitors as epigenetic modulators of Tregs in this review in detail.
Highlights
Regulatory T cells (Tregs) are important to guarantee immunological self-tolerance and homeostasis
We found that a prevention of cecal ligation and puncture (CLP)-dependent liver damage was associated with a decreased number of liver localized Tregs [66]
It has been shown that the differentiation of human CD25highFoxp3+ Tregs into IL-17 producing cells can be prevented by the HDAC inhibitors (HDACi) trichostatin A (TSA) [145]
Summary
Regulatory T cells (Tregs) are important to guarantee immunological self-tolerance and homeostasis. A system must exist that restricts activity of these cells This was proven by the classical thymectomy experiment in neonate mice, which showed T cell-dependent autoimmunity when the thymus was removed at day three after birth but not at day one or day seven [8,9,10]. These tTregs, which migrate to the periphery after day three, are essential for self-tolerance. Foxp binding results in both the activation and repression of its target genes This was determined by chromatin immunoprecipitation (ChIP) against epigenetic markers such as acetylated H3K9/14 (AcH3), tri-methyl H3K4 (Me3K4), and tri-methyl H3K27 (Me3K27). Epigenetic modifications are an interesting approach to cope with these opposite tasks
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