DNA Methylation in Regulatory T Cell Differentiation and Function: Challenges and Opportunities

Bai, Lu; Hao, Xiaolei; Keith, Julia; Feng, Yang

doi:10.3390/biom12091282

Cited by 14 publications

(5 citation statements)

References 150 publications

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“…In contrast, strong T‐cell receptor signaling suppresses miR‐148a to derepress DNMT1 mRNA translation 37 . Thus, accumulating evidence supports the view that DNA methylation plays a key role in Treg cell differentiation and function 38 and, as previously postulated by Melnik et al, breast milk‐derived activation of such pathways may work to increase the expression of Foxp3 39 . Indeed, a study by Golan‐Gerstl et al 40 provides experimental evidence that human breast milk‐derived exosomes can increase miR‐148a in cell cultures, with subsequent DNMT1 suppression.…”

Section: Discussionmentioning

confidence: 95%

Immune‐related microRNAs in breast milk and their relation to regulatory T cells in breastfed children

Ahlberg

Martí

Govindaraj

et al. 2023

Pediatric Allergy Immunology

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Section: Discussionmentioning

confidence: 95%

Immune‐related microRNAs in breast milk and their relation to regulatory T cells in breastfed children

Ahlberg

Martí

Govindaraj

et al. 2023

Pediatric Allergy Immunology

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“…Blood leukocytes also play a significant role in inflammation response and immune cell activation [ 103 – 105 ]. Methylation can influence the expression of immune-related genes in leukocytes, including antigen-presenting genes, immune checkpoint genes, and effector molecules of cytotoxic T cells, with profound implications for immune evasion, and immune suppression [ 106 , 107 ]. Furthermore, this study revealed that the calcium signaling pathway is the most significantly enriched pathway.…”

Section: Discussionmentioning

confidence: 99%

Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study

Wang,

Zhao,

et al. 2024

BMC Med

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Background Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. Methods This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. Results The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. Conclusions This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.

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“…Likewise, altered DNA methylation can control IL-2 expression, which mediates the activation of T cells [91]. Notably, DNA methylation profiles are crucial for the stability of Treg cells and maintaining the steady expression of FOXP3 protein [92], and higher FOXP3 protein levels were associated with worse allograft outcomes and diabetic pathogenesis [93,94].…”

Section: St Author and Year Type Of Study Ptdm Definition Population ...mentioning

confidence: 99%

Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus

Abdelrahman,

Maxwell,

McKnight

2024

Genes

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Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation. PTDM prevalence varies due to different diabetes definitions. Consensus guidelines for the diagnosis of PTDM have been published based on random blood glucose levels, glycated hemoglobin (HbA1c), and oral glucose tolerance test (OGTT). The task of diagnosing PTDM continues to pose challenges, given the potential for diabetes to manifest at different time points after transplantation, thus demanding constant clinical vigilance and repeated testing. Interpreting HbA1c levels can be challenging after renal transplantation. Pre-transplant risk factors for PTDM include obesity, sedentary lifestyle, family history of diabetes, ethnicity (e.g., African-Caribbean or South Asian ancestry), and genetic risk factors. Risk factors for PTDM include immunosuppressive drugs, weight gain, hepatitis C, and cytomegalovirus infection. There is also emerging evidence that genetic and epigenetic variation in the organ transplant recipient may influence the risk of developing PTDM. This review outlines many known risk factors for PTDM and details some of the pathways, genetic variants, and epigenetic features associated with PTDM. Improved understanding of established and emerging risk factors may help identify people at risk of developing PTDM and may reduce the risk of developing PTDM or improve the management of this complication of organ transplantation.

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DNA Methylation in Regulatory T Cell Differentiation and Function: Challenges and Opportunities

Cited by 14 publications

References 150 publications

Immune‐related microRNAs in breast milk and their relation to regulatory T cells in breastfed children

Immune‐related microRNAs in breast milk and their relation to regulatory T cells in breastfed children

Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study

Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus

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