FoxP3 in Treg cell biology: a molecular and structural perspective

Deng, Guoping; Song, Xiaomin; Greene, Mark I.

doi:10.1111/cei.13357

Cited by 32 publications

(20 citation statements)

References 71 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Functions of FoxP3 + T-cells are fundamental to the development and maintenance of immune tolerance [25]. FoxP3 + T-cells are involved in maintaining immunological tolerance toward host tissues and considered to be suppressors of anti-tumor immune responses [25]. Thus, the presence of FoxP3 + T-cells in the tumor microenvironment would indicate an unfavorable prognosis [26,27].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of FoxP3 and CTLA-4 expression in patients with oral squamous cell carcinoma

et al. 2020

View full text Add to dashboard Cite

Background Tumor-infiltrating lymphocytes include tumor-reactive lymphocytes and regulatory T-cells. However, the prognostic value of tumor-infiltrating lymphocytes in oral squamous cell carcinoma (OSCC) remains unclear. Methods We used immunohistochemistry to evaluate the presence of tumor-infiltrating FoxP3⁺ T-cells and CTLA-4⁺ cells in four distinct histological compartments (tumor parenchyma and stroma at the tumor center, and parenchyma and stroma at the invasive front) and assessed the association between the prevalence of these cells and the histopathological status of 137 patients with OSCC. Results Five-year overall survival, disease-specific survival, and recurrence-free survival were favorable in patients with high numbers of FoxP3⁺ T-cells in the parenchyma of the invasive front. Recurrence-free survival and metastasis-free survival were decreased in patients with high numbers of CTLA-4⁺ cells in the parenchyma of the invasive front. Conclusions The presence of FoxP3⁺ T-cells in the parenchyma of the invasive front may be a useful prognostic factor. Our results indicate that FoxP3⁺ T-cells may exert site-specific anti-tumor effects but may not play an immunosuppressive role in OSCC. In addition, our results suggest that CTLA-4 + cells suppress the function of FoxP3 + T-cells and promote anti-tumor immunity in OSCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Prognostic value of FoxP3 and CTLA-4 expression in patients with oral squamous cell carcinoma

et al. 2020

View full text Add to dashboard Cite

show abstract

“…A recent study by Bin Dhuban et al elegantly shows that some inheritable mutations in the forkhead domain of FOXP3 can specifically disrupt FOXP3-TIP60 association, in turn, compromising human Treg cell development and function. Restoring FOXP3-TIP60 in this setting with allosteric modification of TIP60 also rescued Treg cell function (117, 118).…”

Section: Post-translational Modifications Of Foxp3mentioning

confidence: 94%

Foxp3 Post-translational Modifications and Treg Suppressive Activity

et al. 2019

View full text Add to dashboard Cite

Regulatory T cells (Tregs) are engaged in maintaining immune homeostasis and preventing autoimmunity. Treg cells include thymic Treg cells and peripheral Treg cells, both of which can suppress the immune response via multiple distinct mechanisms. The differentiation, proliferation, suppressive function and survival of Treg cells are affected by distinct energy metabolic programs. Tissue-resident Treg cells hold unique features in comparison with the lymphoid organ Treg cells. Foxp3 transcription factor is a lineage master regulator for Treg cell development and suppressive activity. Accumulating evidence indicates that the activity of Foxp3 protein is modulated by various post-translational modifications (PTMs), including phosphorylation, O-GlcNAcylation, acetylation, ubiquitylation and methylation. These modifications affect multiple aspects of Foxp3 function. In this review, we define features of Treg cells and roles of Foxp3 in Treg biology, and summarize current research in PTMs of Foxp3 protein involved in modulating Treg function. This review also attempts to define Foxp3 dimer modifications relevant to mediating Foxp3 activity and Treg suppression. Understanding Foxp3 protein features and modulation mechanisms may help in the design of rational therapies for immune diseases and cancer.

show abstract

“…It has been established that the expression of FOXP3 on CD4+ cells can be used as a typical marker of Tregs. 30 Low expression and absence of CD127 expression on CD4+CD25+Tregs can serve as an alternative to FOXP3 expression on CD4+CD25+ T cells. 31 FOXP3+Tregs have been documented in many diseases such as organ transplantation, systemic lupus erythematosus, cancer, and ACS.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of TIGIT Expression in FOXP3+Regulatory T Cells in Acute Coronary Syndrome

Xiong¹,

Luo²,

Zhou³

et al. 2022

JIR

View full text Add to dashboard Cite

Objective Little is currently known on the role of T-cell immunoglobulin and ITIM domain (TIGIT) expression in Foxp3+ regulatory T cells (TIGIT+Tregs) in acute coronary syndrome (ACS) patients. The aim of this study was to investigate the role and alterations of TIGIT+Tregs in ACS patients. Methods We enrolled 117 subjects, including 61 ACS patients, 26 chronic coronary syndrome (CCS) patients, and 30 control subjects without coronary artery disease. The quantification of TIGIT+Tregs was determined by flow cytometry; serum interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) were also measured. Results TIGIT+Tregs expression was significantly lower in ACS patients compared with CCS and control patients (P<0.05). The expression of TIGIT+Tregs was comparable in patients with and without traditional risk factors (P>0.05). Logistic regression analysis revealed that TIGIT+Tregs levels are independent predictors of ACS (P<0.01). Receiver-operating characteristic (ROC) curve analysis showed the expression levels of TIGIT+Tregs had a discriminative power for ACS (P<0.01). IL-6 levels were increased (P<0.01), while TGF-β was decreased in ACS patients compared with CCS and control patients (P<0.01). Meanwhile, an inverse correlation between IL-6 and TIGIT+Tregs was observed (P<0.01), while a positive correlation between TGF-β and TIGIT+Tregs was found (P<0.05). Conclusion TIGIT+Tregs levels are significantly reduced in ACS, accompanied by upregulated IL-6 and downregulated TGF-β expression. The downregulated TIGIT+Tregs are independent predictors of ACS. These findings suggest that TIGIT+Tregs may have an anti-inflammatory and protective effect on ACS, and its decreased expression may be associated with atherosclerotic plaque destabilization.

show abstract

FoxP3 in Treg cell biology: a molecular and structural perspective

Cited by 32 publications

References 71 publications

Prognostic value of FoxP3 and CTLA-4 expression in patients with oral squamous cell carcinoma

Prognostic value of FoxP3 and CTLA-4 expression in patients with oral squamous cell carcinoma

Foxp3 Post-translational Modifications and Treg Suppressive Activity

Downregulation of TIGIT Expression in FOXP3+Regulatory T Cells in Acute Coronary Syndrome

Contact Info

Product

Resources

About