New Insights into Epigenetic Regulation of T Cell Differentiation

Dutta, Avik; Venkataganesh, Harini; Love, Paul E.

doi:10.3390/cells10123459

Cited by 28 publications

(18 citation statements)

References 116 publications

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“…T-cell reprogramming creates a new therapeutic option that may be tested to a large extent without the exploitation of animal models. Since epigenetics appears to be a common denominator for hormonal and immunological aberrations in endometriosis, adjustment of hormonal imbalances and influencing T-cell development, differentiation, and activation should be considered (12,21,38,354,355). Epigenetic, reversible regulation of Tregs toward higher ectopic endometrial cell detectability, and elimination can be a significant step in human treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Analogously, histone methyltransferases and deacetylases are associated with the silencing of gene expression, and histone demethylases and acetyltransferases promote gene expression (94). In addition, difficult to predict in an individual case, the effects of inadequate methylation/demethylation and acetylation/deacetylation on the chromatin conformation should be considered (21,98).…”

Section: Epigenetic Mechanisms Influencing Tcr Signaling and Autoimmu...mentioning

confidence: 99%

“…Activated naïve CD4+ T cells are highly plastic cells that can differentiate into various Th-cell fates characterized by the expression of effector cytokines such as IFN-g (Th1), IL-4 (Th2) or IL-17A (Th17). Thus, epigenetic modifications greatly influence the functional differentiation of T-cell subsets, including linage commitment to short-lived effectors, long-term memory T cells, T regulatory cells, and other specific T-cell populations (21). The pattern of DNA methylation at key cytokine (IL-2, IL-4) loci influences the control of CD4+ T-cell differentiation and postthymic T-cell maturation (122).…”

Section: Epigenetic Reprogramming Of T Cells In Autoimmune Diseasesmentioning

confidence: 99%

“…On the other hand, a T-cell subpopulation named regulatory T cells (Tregs) is essential to maintain immune homeostasis and prevent autoimmune disorders (19,20). It has been proven that the entire population of T cells is subjected to epigenetic mechanisms that largely govern its maturation and differentiation (21,22). Thus, precise identification of functional epigenetic pathways in T-cell maturation/ differentiation and the modifiers responsible for dysregulation of these processes may provide further insight into the nature of autoimmunity in the context of therapeutic methods.…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity

Szukiewicz

2022

Front. Immunol.

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Endometriosis is defined as the presence of endometrial-like glands and stroma located outside the uterine cavity. This common, estrogen dependent, inflammatory condition affects up to 15% of reproductive-aged women and is a well-recognized cause of chronic pelvic pain and infertility. Despite the still unknown etiology of endometriosis, much evidence suggests the participation of epigenetic mechanisms in the disease etiopathogenesis. The main rationale is based on the fact that heritable phenotype changes that do not involve alterations in the DNA sequence are common triggers for hormonal, immunological, and inflammatory disorders, which play a key role in the formation of endometriotic foci. Epigenetic mechanisms regulating T-cell responses, including DNA methylation and posttranslational histone modifications, deserve attention because tissue-resident T lymphocytes work in concert with organ structural cells to generate appropriate immune responses and are functionally shaped by organ-specific environmental conditions. Thus, a failure to precisely regulate immune cell transcription may result in compromised immunological integrity of the organ with an increased risk of inflammatory disorders. The coexistence of endometriosis and autoimmunity is a well-known occurrence. Recent research results indicate regulatory T-cell (Treg) alterations in endometriosis, and an increased number of highly active Tregs and macrophages have been found in peritoneal fluid from women with endometriosis. Elimination of the regulatory function of T cells and an imbalance between T helper cells of the Th1 and Th2 types have been reported in the endometria of women with endometriosis-associated infertility. This review aims to present the state of the art in recognition epigenetic reprogramming of T cells as the key factor in the pathophysiology of endometriosis in the context of T-cell-related autoimmunity. The new potential therapeutic approaches based on epigenetic modulation and/or adoptive transfer of T cells will also be outlined.

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Section: Discussionmentioning

confidence: 99%

Section: Epigenetic Mechanisms Influencing Tcr Signaling and Autoimmu...mentioning

confidence: 99%

Section: Epigenetic Reprogramming Of T Cells In Autoimmune Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity

Szukiewicz

2022

Front. Immunol.

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“…Treg cells are essential regulators of immune homeostasis, characterized by a distinct pattern of gene expression and epigenetic modifications that includes upregulation of immune suppressive genes and downregulation of inflammatory genes [15]. Epigenetic changes, however, are not specific attributes of Treg cells, since they greatly influence the function and differentiation of all CD4 + T cell subsets [16][17][18]. Although Treg cells are not an homogenous population, the transcription factor forkhead box P3 (FOXP3) is considered as the master regulator of Treg cell differentiation, maintenance and function [19,20].…”

Section: Introductionmentioning

confidence: 99%

Absent in Melanoma 2 (AIM2) Regulates the Stability of Regulatory T Cells

Lozano-Ruiz

Tzoumpa

Martínez-Cardona

et al. 2022

IJMS

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Absent in melanoma 2 (AIM2) is a cytosolic dsDNA sensor that has been broadly studied for its role in inflammasome assembly. However, little is known about the function of AIM2 in adaptive immune cells. The purpose of this study was to investigate whether AIM2 has a cell-intrinsic role in CD4+ T cell differentiation or function. We found that AIM2 is expressed in both human and mouse CD4+ T cells and that its expression is affected by T cell receptor (TCR) activation. Naïve CD4+ T cells from AIM2-deficient (Aim2−/−) mice showed higher ability to maintain forkhead box P3 (FOXP3) expression in vitro, while their capacity to differentiate into T helper (Th)1, Th2 or Th17 cells remained unaltered. Transcriptional profiling by RNA sequencing showed that AIM2 might affect regulatory T cell (Treg) stability not by controlling the expression of Treg signature genes, but through the regulation of the cell’s metabolism. In addition, in a T cell transfer model of colitis, Aim2−/−-naïve T cells induced less severe body weight loss and displayed a higher ability to differentiate into FOXP3+ cells in vivo. In conclusion, we show that AIM2 function is not confined to innate immune cells but is also important in CD4+ T cells. Our data identify AIM2 as a regulator of FOXP3+ Treg cell differentiation and as a potential intervention target for restoring T cell homeostasis.

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Metabolic dialogues: regulators of chimeric antigen receptor T cell function in the tumor microenvironment

Moraly,

Kondo,

Benzaoui

et al. 2024

Molecular Oncology

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Tumor‐infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T cells have demonstrated remarkable success in the treatment of relapsed/refractory melanoma and hematological malignancies, respectively. These treatments have marked a pivotal shift in cancer management. However, as “living drugs,” their effectiveness is dependent on their ability to proliferate and persist in patients. Recent studies indicate that the mechanisms regulating these crucial functions, as well as the T cell's differentiation state, are conditioned by metabolic shifts and the distinct utilization of metabolic pathways. These metabolic shifts, conditioned by nutrient availability as well as cell surface expression of metabolite transporters, are coupled to signaling pathways and the epigenetic landscape of the cell, modulating transcriptional, translational, and post‐translational profiles. In this review, we discuss the processes underlying the metabolic remodeling of activated T cells, the impact of a tumor metabolic environment on T cell function, and potential metabolic‐based strategies to enhance T cell immunotherapy.

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New Insights into Epigenetic Regulation of T Cell Differentiation

Cited by 28 publications

References 116 publications

Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity

Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity

Absent in Melanoma 2 (AIM2) Regulates the Stability of Regulatory T Cells

Metabolic dialogues: regulators of chimeric antigen receptor T cell function in the tumor microenvironment

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