Down-regulation of Tet2 is associated with Foxp3 TSDR hypermethylation in regulatory T cell of allergic rhinitis

Tan, Lu; Qiu, Ting; Xiang, Rong; Cao, Cheng; Deng, Yuxiao; Tao, Zezhang; Xu, Yu

doi:10.1016/j.lfs.2019.117101

Cited by 18 publications

(18 citation statements)

References 49 publications

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“…The Foxp3 gene mutation can cause CD4 + CD25 + Foxp3 + Treg deficiency, results in X‐linked syndrome, immune dysregulation, enteropathy, and polyendocrinopathy, which is similar to human Scurfy [25]. It has been found that the CD4 + CD25 + Foxp3 + Treg frequency is lower in patients with asthma [26], allergic rhinitis [27], and FA [28]. Thus, to identify causative factors for the Treg reduction in patients with allergic disorders is of significance.…”

Section: Discussionmentioning

confidence: 99%

Modulating oxidative stress counteracts specific antigen‐induced regulatory T‐cell apoptosis in mice

et al. 2021

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Treg are known to have a central role in orchestrating immune responses, but less is known about the destiny of Treg after being activated by specific Ags. This study aimed to investigate the role of superoxide dismutase, an active molecule in the regulation of oxidative stress in the body, in the prevention of Treg apoptosis induced by specific Ags. Ag‐specific Tregs were isolated from the DO11.10 mouse intestine. A food allergy mouse model was developed with ovalbumin as the specific Ag and here, we observed that exposure to specific Ag induced Treg apoptosis through converting the precursor of TGF‐β to its mature form inside the Tregs. Oxidative stress was induced in Tregs upon exposure to specific Ags, in which Smad3 bound the latency‐associated peptide to induce its degradation, converting the TGF‐β precursor to its mature form, TGF‐β. Suppressing oxidative stress in Tregs alleviated the specific Ag‐induced Treg apoptosis in in vitro experiments and suppressed experimental food allergy by preventing the specific Ag‐induced Treg apoptosis in the intestine. In conclusion, exposure to specific Ags induces Treg apoptosis and it can be prevented by upregulating superoxide dismutase or suppressing reactive oxidative species in Tregs.

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Section: Discussionmentioning

confidence: 99%

Modulating oxidative stress counteracts specific antigen‐induced regulatory T‐cell apoptosis in mice

et al. 2021

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“…Patients were experiencing an allergic episode at the time of recruitment and had come to the hospital for medical assistance. Notably, no patient included in the present study had been treated with specific immunotherapy, or received antibiotics, steroids, antihistamines or immune drugs in the 4 weeks prior to recruitment (15,16). The epithelial samples were gently scraped from the surface of the inferior nasal turbinate using a plastic curette and were quickly stored at -80˚C.…”

Section: Methodsmentioning

confidence: 99%

miR-31 attenuates murine allergic rhinitis by suppressing interleukin-13-induced nasal epithelial inflammatory responses

Zhou

Liu

et al. 2020

Mol Med Rep

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“…Base modifications include primarily methylation/hydroxylmethylation demethylation of cytosine and adenosine. DNA methylation refers to the addition of a methyl group to cytosine or adenosine generating 5-methylcytosine (5mC), which is catalyzed by DNA methyltransferases (DNMTs) [ 16 ]. There are three types of DNMTs (DNMT1, DNMT3a, and DNMT3b); each of which play a unique role in DNA methylation.…”

Section: Mechanisms and Significance Of Treg Methylationmentioning

confidence: 99%

“…During the development of nTreg cells, IL-2 has been shown to play an important role in Tet2 upregulation, which is essential for stable Foxp3 expression ( Figure 2 ) [ 23 ]. In this context, Foxp3 TSDR methylation is inversely correlated with Tet2 and Foxp3 expression; however, the level of Foxp3 expression is proportionate to the percentage of Treg cells [ 16 ]. Taken together, Tet family members promote nTreg cell stability and immune homeostasis by regulating Foxp3 epigenetic modifications.…”

Section: Mechanisms and Significance Of Treg Methylationmentioning

confidence: 99%

“…Aberrant Foxp3 methylation has been associated with the downregulation of Tet2, which primarily regulated the demethylation of gene bodies. Indeed, Foxp3 mRNA and protein levels were significantly reduced in the Treg cells of AR patients relative to normal controls [ 16 ]. Consistently, Tet2 expression was also downregulated in AR, suggesting that Tet2 modulated Treg cell function through the regulation of Foxp3 methylation.…”

Section: Mechanisms and Significance Of Treg Methylationmentioning

confidence: 99%

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Contribution of Regulatory T Cell Methylation Modifications to the Pathogenesis of Allergic Airway Diseases

Sha

Sun

et al. 2021

Journal of Immunology Research

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Regulatory T (Treg) cells are a subtype of CD4+ T cells that play a significant role in the protection from autoimmunity and the maintenance of immune tolerance via immune regulation. Epigenetic modifications of Treg cells (i.e., cytosine methylation at the promoter region of the transcription factor, Forkhead Box P3) have been found to be closely associated with allergic diseases, including allergic rhinitis, asthma, and food allergies. In this study, we highlighted the recent evidence on the contribution of epigenetic modifications in Treg cells to the pathogenesis of allergic diseases. Moreover, we also discussed directions for future clinical treatment approaches, with a particular emphasis on Treg cell-targeted therapies for allergic disorders.

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Down-regulation of Tet2 is associated with Foxp3 TSDR hypermethylation in regulatory T cell of allergic rhinitis

Cited by 18 publications

References 49 publications

Modulating oxidative stress counteracts specific antigen‐induced regulatory T‐cell apoptosis in mice

Modulating oxidative stress counteracts specific antigen‐induced regulatory T‐cell apoptosis in mice

miR-31 attenuates murine allergic rhinitis by suppressing interleukin-13-induced nasal epithelial inflammatory responses

Contribution of Regulatory T Cell Methylation Modifications to the Pathogenesis of Allergic Airway Diseases

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