Mouse Double Minute 2 Homolog-Mediated Ubiquitination Facilitates Forkhead Box P3 Stability and Positively Modulates Human Regulatory T Cell Function

Wang, Aiting; Yang, Mei; Liang, Rui; Zhu, Fangming; Zhu, Fuxiang; Liu, Xinnan; Han, Yichao; Lin, Rongfu; Wang, Xiaoxia; Li, Dan; Li, Hecheng; Yuan, Xiaojun; Zhao, Hui; Li, Bin

doi:10.3389/fimmu.2020.01087

Cited by 14 publications

(9 citation statements)

References 43 publications

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“…Foxp3, a member of the fork-head transcription factor family, is a marker transcription factor of Treg cells. It can affect the growth and development of Treg cells [ 74 ]. Mutations in Foxp3 lead to autoimmune diseases, and defects in Foxp3 lead to intestinal mucosal inflammation.…”

Section: Acupuncture Exerts Immunomodulatory Effects By Regulating Adaptive Immune Systemmentioning

confidence: 99%

A Review on the Immunomodulatory Mechanism of Acupuncture in the Treatment of Inflammatory Bowel Disease

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Inflammatory bowel disease (IBD) is a chronic inflammatory disease with a high prevalence and canceration rate. The immune disorder is one of the recognized mechanisms. Acupuncture is widely used to treat patients with IBD. In recent years, an increasing number of studies have proven the effectiveness of acupuncture in the treatment of IBD, and some progress has been made in the mechanism. In this paper, we reviewed the studies related to acupuncture for IBD and focused on the immunomodulatory mechanism. We found that acupuncture could regulate the innate and adaptive immunity of IBD patients in many ways. Acupuncture exerts innate immunomodulatory effects by regulating intestinal epithelial barrier, toll-like receptors, NLRP3 inflammasomes, oxidative stress, and endoplasmic reticulum stress and exerts adaptive immunomodulation by regulating the balance of Th17/Treg and Th1/Th2 cells. In addition, acupuncture can also regulate intestinal flora.

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Section: Acupuncture Exerts Immunomodulatory Effects By Regulating Adaptive Immune Systemmentioning

confidence: 99%

A Review on the Immunomodulatory Mechanism of Acupuncture in the Treatment of Inflammatory Bowel Disease

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…In addition, TNF receptor associated factor 6 (TRAF6) is demonstrated to mediate K63-linked polyubiquitination of FOXP3, which is a kind of nonproteolytic ubiquitination. In Treg, TRAF6-mediated polyubiquitination directs the proper localization of FOXP3 and stabilizes [63].…”

Section: Posttranslational Modifications Of Foxp3mentioning

confidence: 99%

“…Elevated expression of RNF31 in human Treg cells is associated with a stronger immune‐suppressive capacity [62]. Mouse double minute 2 homolog (MDM2) can also increase the suppressive function of Tregs by ubiquitinating and stabilizing FOXP3 [63].…”

Section: Posttranslational Modifications Of Foxp3mentioning

confidence: 99%

Transcriptional and posttranslational regulation of Th17/Treg balance in health and disease

et al. 2021

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Regulatory T (Treg) cells and T helper type 17 (Th17) cells play important roles in adaptive immune responses, antagonizing each other in immune disorders. Th17/Treg balance is critical to maintaining the immune homeostasis of human bodies and is tightly regulated under healthy conditions. The transcription factors that are required for driving Th17 and Treg cell lineages differentiation respectively, RORγt and FOXP3 are tightly regulated under different tissue microenvironment, especially the transcriptional induction, posttranslational modifications, and dynamic enzymatic cofactors binding. The imbalance caused by alteration of the quantity or properties of RORγt + Th17 or FOXP3 + Treg can contribute to inflammatory disorders in humans. Restoring Th17/Treg balance by modifying the enzymatic activities of RORγt and FOXP3 binding partners may be therapeutically applied to treat severe immune disorders. In this review, we focus on the transcriptional and posttranslational regulations of Th17/Treg balance, immune disorders caused by Th17/Treg imbalance, and new therapeutic strategies for restoring immune homeostasis.

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“…As the key regulator of Treg cells, FOXP3 protein level determines Treg cell identification and function [3]. Foxp3 undergoes ubiquitination and proteasome‐mediated degradation, including STUB1‐HSP70 promotes FOXP3 K48 linked ubiquitination under IL‐6 and LPS stimulation, TRAF6 mediates FXO3 K63 linked ubiquitination and directs FOXP3 localization, and MDM2 catalyzes FOXP3 monoubiquitination, as well as K63‐, K29‐, and K33‐linked polyubiquitination [11,152,164]. USP21 mediates FOXP3 deubiquitination and prevents FOXP3 degradation [10].…”

Section: Foxp3 Modificationsmentioning

confidence: 99%

FOXP3⁺ regulatory T cells and age‐related diseases

et al. 2021

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Regulatory T (Treg) cells are critical for the maintenance of immune homeostasis. Dysregulation of Treg cells has been implicated in the pathogenesis of autoimmunity and chronic inflammation, while aging is characterized by an accumulation of inflammatory markers in the peripheral blood, a phenomenon known as 'inflammaging'. The relationship between Treg cells and age-related diseases remains to be further studied. Increasing evidence revealed that Treg cells' dysfunction occurs in aged patients, suggesting that immune therapies targeting Treg cells may be a promising approach to treat diseases such as cancers and autoimmune diseases. Furthermore, drugs targeting Treg cells show encouraging results and contribute to CD8 + T-cell-mediated cytotoxic killing of tumor and infected cells. In general, a better understanding of Treg cell function may help us to develop new immune therapies against aging. In this review, we discuss potential therapeutic strategies to modify immune responses of relevance for aging to prevent and treat age-related diseases, as well as the challenges posed by the translation of novel immune therapies into clinical practice.

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Mouse Double Minute 2 Homolog-Mediated Ubiquitination Facilitates Forkhead Box P3 Stability and Positively Modulates Human Regulatory T Cell Function

Cited by 14 publications

References 43 publications

A Review on the Immunomodulatory Mechanism of Acupuncture in the Treatment of Inflammatory Bowel Disease

A Review on the Immunomodulatory Mechanism of Acupuncture in the Treatment of Inflammatory Bowel Disease

Transcriptional and posttranslational regulation of Th17/Treg balance in health and disease

FOXP3⁺ regulatory T cells and age‐related diseases

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Mouse Double Minute 2 Homolog-Mediated Ubiquitination Facilitates Forkhead Box P3 Stability and Positively Modulates Human Regulatory T Cell Function

Cited by 14 publications

References 43 publications

A Review on the Immunomodulatory Mechanism of Acupuncture in the Treatment of Inflammatory Bowel Disease

A Review on the Immunomodulatory Mechanism of Acupuncture in the Treatment of Inflammatory Bowel Disease

Transcriptional and posttranslational regulation of Th17/Treg balance in health and disease

FOXP3+ regulatory T cells and age‐related diseases

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Product

Resources

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FOXP3⁺ regulatory T cells and age‐related diseases