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Review
. 2023 Oct 2;19(16):5120-5144.
doi: 10.7150/ijbs.88327. eCollection 2023.

Epigenetic modulations of immune cells: from normal development to tumor progression

Yuanchun Xu  1   2 , Zongsheng He  3 , Jing Du  1 , Ziqiang Chen  1 , John W M Creemers  4 , Bin Wang  3 , Fan Li  1 , Yaling Wang  2
Affiliations
Review

Epigenetic modulations of immune cells: from normal development to tumor progression

Yuanchun Xu et al. Int J Biol Sci. .

Abstract

The dysfunction of immune cell development often impairs immunological homeostasis, thus causing various human diseases. Accumulating evidence shows that the development of different immune cells from hematopoietic stem cells are highly fine-tuned by different epigenetic mechanisms including DNA methylation, histone modifications, chromatin remodeling and RNA-related regulations. Understanding how epigenetic regulators modulate normal development of immune cells contributes to the identification of new strategies for various diseases. Here, we review recent advances suggesting that epigenetic modulations can orchestrate immune cell development and functions through their impact on critical gene expression. We also discuss the aberrations of epigenetic modulations in immune cells that influence tumor progression, and the fact that underlying mechanisms affect how epigenetic drugs interfere with tumor progression in the clinic.

Keywords: DNA methylation; Innate immune cells; RNA-associated modulations; adaptive immune cells; cancer treatment; chromatin remodeling; histone modifications.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Schematic model of four epigenetic modifications. Chromatin remodeling allows TFs or other DNA binding proteins to access DNA and control gene expression by the rearranging chromatin from a closed state to an open state. There are four major types of Chromatin remodeler: INO80, NuRD, ISWI and SWI/SNF family. The effects of histone modifications on gene expression could differ from type to type. We list four common types of histone modifications including histone acetylation (Ac), histone methylation (Me), histone phosphorylation (P) and histone ubiquitination (Ub). DNA methylation often exists in GC-rich areas of the human genome called CpG islands, which can be methylated by DNMTs, resulting in repression of transcription of genes. In contrast, DNA demethylation function as opposite effects on the transcription of genes. When DNA transcribed into RNAs, the RNAs can be methylated in a reversible manner, which regulates their translation, stability and decay. Furthermore, many DNA sequences are not transcribed into mRNAs but are transcribed as ncRNAs. Based on the length, ncRNAs can be divided into short and long ncRNAs (lncRNAs). Short ncRNAs are less than 200 bp in length, including microRNAs (miRNAs), small interfering RNAs (siRNAs), PIWI-interacting RNAs (piRNAs), etc. lncRNAs are more than 200 bp in length. They target the 3'-UTR of mRNA, thus causing gene silencing.
Figure 2
Figure 2
The role of epigenetic modifications in the differentiation, development and activity of immune cells. Hematopoietic stem cells (HSCs) produce all blood cell types including myeloid progenitors (MPs) and lymphoid progenitors (LPs). Here we majorly introduce three myeloid cells include macrophages, neutrophils and dendritic cells and lymphoid cells include T cells, B cells and natural killer cells. Four epigenetic modifications are indicated for differentiation, development and activity of immune cells. NKs: natural killer cells, DCs: dendritic cells, M1: M1-like macrophages, M2: M2-like macrophages, Th: T helper. ①-④ represent different type of epigenetic modifications.
Figure 3
Figure 3
The epigenetic modifications of immune cells in tumor microenvironment. A. The epigenetic modifications of adaptive immune cells (B and T cells) in tumor progression. Different epigenetic modulators like histone methylation regulator H3K27me3 and DNA methylation regulator DNMT1 have been shown to regulate development and/ or activity of immune cells in distinct tumor progression. On the other hand, the effect of epigenetic modulation like histone deacetylation regulator HDAC on tumor cells could also regulate infiltration of immune cells into TME by regulating the expression of genes like PD-L1 and HLA-DR on tumor cells. B. The epigenetic modifications of innate immune cells (NKs, macrophages, neutrophils and DCs) in tumor progression. Different epigenetic modulators like histone methylation regulator H3K79me2 and microRNAs have been shown to regulate development and/ or activity of immune cells in distinct tumor t ypes. Meanwhile, many epigenetic regulators like DNA methylation regulator TET2 and miR-93, regulating IL-1R and ULBP3 expression in the tumor cells, respectively, which impact on tumor progression. The genes marked in red represent the effect of epigenetic modulations on expression of genes in tumor cells, while the genes marked in black represent the effect of epigenetic modulations on expression of genes in immune cells. In both cases, the expression of these genes interferes with tumor progression by immune cells. Arrows (↑) illustrate promoting and blunt ended lines (┬) dictate inhibiting effects.
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References

    1. Baylin SB, Jones PA. Epigenetic Determinants of Cancer. Cold Spring Harb Perspect Biol. 2016;8:a019505. - PMC - PubMed
    1. Mazzone R, Zwergel C, Artico M, Taurone S, Ralli M, Greco A. et al. The emerging role of epigenetics in human autoimmune disorders. Clin Epigenetics. 2019;11:1–15. - PMC - PubMed
    1. Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H, Merad M. et al. Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment. Cell. 2014;159:1312–26. - PMC - PubMed
    1. Sen DR, Kaminski J, Barnitz RA, Kurachi M, Gerdemann U, Yates KB. et al. The epigenetic landscape of T cell exhaustion. Science. 2016;354:1165–9. - PMC - PubMed
    1. Adoue V, Binet B, Malbec A, Fourquet J, Romagnoli P, van Meerwijk JPM. et al. The Histone Methyltransferase SETDB1 Controls T Helper Cell Lineage Integrity by Repressing Endogenous Retroviruses. Immunity. 2019;50:629–644.e8. - PubMed

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