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Cells
Special Issues
Regulatory T Cells and Autoimmunity
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Regulatory T Cells and Autoimmunity

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: 10 February 2025 | Viewed by 4163

Special Issue Editor

Dr. Fan Pan

E-Mail Website
Guest Editor
Center for Cancer Immunology Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
Interests: inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The intricate balance between immune defense and self-tolerance is a fundamental pillar of our immune system. It prevents the immune system from attacking the body's tissues and controls excessive immune responses that could harm the host. This equilibrium is maintained by regulatory T cells (Tregs) and specialized CD4+ T cells that express forkhead box transcription factor (Foxp3), which perform immunosuppressive functions. Tregs are indispensable for upholding immune stability and preventing autoimmune reactions, making them vital participants in immune homeostasis and self-tolerance. A dysregulation of Tregs reduces their immunosuppressive functions, ultimately triggering the onset and progression of numerous autoimmune diseases.

The therapeutic potential of Tregs has been demonstrated in preclinical models of autoimmune diseases. However, significant scientific and clinical challenges must be addressed before Treg-based therapies can be widely implemented. It is therefore crucial to understand the function of Tregs in regulating immune responses during autoimmune diseases and reinstating self-tolerance. This is valuable for gaining deeper insights into the mechanisms behind Treg dysfunction in autoimmunity and enhancing the effectiveness of Treg-based therapies.

This Special Issue aims to highlight recent advances in the role of Tregs in autoimmune diseases. We encourage contributions that explore the cellular and molecular aspects of CD4+Foxp3+ Treg development, maintenance, and function, with a central focus on the evolving landscape of Treg-based therapeutic approaches in autoimmune disease.

Dr. Fan Pan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • regulatory T cells
  • immune tolerance
  • Foxp3
  • autoimmune disease (AD)
  • immunotherapy

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Published Papers (2 papers)

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Research

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26 pages, 5949 KiB  
Article
Modulation of Suppressive Activity and Proliferation of Human Regulatory T Cells by Splice-Switching Oligonucleotides Targeting FoxP3 Pre-mRNA
by Varvara G. Blinova, Yulia A. Gladilina, Anna A. Abramova, Daria D. Eliseeva, Valentina V. Vtorushina, Anastasia N. Shishparenok and Dmitry D. Zhdanov
Cells 2024, 13(1), 77; https://doi.org/10.3390/cells13010077 - 29 Dec 2023
Cited by 4 | Viewed by 2499
Abstract
The maturation, development, and function of regulatory T cells (Tregs) are under the control of the crucial transcription factor Forkhead Box Protein 3 (FoxP3). Through alternative splicing, the human FoxP3 gene produces four different splice variants: a full-length variant (FL) and truncated variants [...] Read more.
The maturation, development, and function of regulatory T cells (Tregs) are under the control of the crucial transcription factor Forkhead Box Protein 3 (FoxP3). Through alternative splicing, the human FoxP3 gene produces four different splice variants: a full-length variant (FL) and truncated variants with deletions of each of exons 2 (∆2 variant) or 7 (∆7 variant) or a deletion of both exons (∆2∆7 variant). Their involvement in the biology of Tregs as well as their association with autoimmune diseases remains to be clarified. The aim of this work was to induce a single FoxP3 splice variant in human Tregs by splice switching oligonucleotides and to monitor their phenotype and proliferative and suppressive activity. We demonstrated that Tregs from peripheral blood from patients with multiple sclerosis preferentially expressed truncated splice variants, while the FL variant was the major variant in healthy donors. Tregs with induced expression of truncated FoxP3 splice variants demonstrated lower suppressive activity than those expressing FL variants. Reduced suppression was associated with the decreased expression of Treg-associated suppressive surface molecules and the production of cytokines. The deletion of exons 2 and/or 7 also reduced the cell proliferation rate. The results of this study show an association between FoxP3 splice variants and Treg function and proliferation. The modulation of Treg suppressive activity by the induction of the FoxP3 FL variant can become a promising strategy for regenerative immunotherapy. Full article
(This article belongs to the Special Issue Regulatory T Cells and Autoimmunity)
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Review

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34 pages, 2379 KiB  
Review
Many Faces of Regulatory T Cells: Heterogeneity or Plasticity?
by Varvara G. Blinova and Dmitry D. Zhdanov
Cells 2024, 13(11), 959; https://doi.org/10.3390/cells13110959 - 1 Jun 2024
Cited by 1 | Viewed by 1294
Abstract
Regulatory T cells (Tregs) are essential for maintaining the immune balance in normal and pathological conditions. In autoimmune diseases and transplantation, they restrain the loss of self-tolerance and promote engraftment, whereas in cancer, an increase in Treg numbers is mostly associated with tumor [...] Read more.
Regulatory T cells (Tregs) are essential for maintaining the immune balance in normal and pathological conditions. In autoimmune diseases and transplantation, they restrain the loss of self-tolerance and promote engraftment, whereas in cancer, an increase in Treg numbers is mostly associated with tumor growth and poor prognosis. Numerous markers and their combinations have been used to identify Treg subsets, demonstrating the phenotypic diversity of Tregs. The complexity of Treg identification can be hampered by the unstable expression of some markers, the decrease in the expression of a specific marker over time or the emergence of a new marker. It remains unclear whether such phenotypic shifts are due to new conditions or whether the observed changes are due to initially different populations. In the first case, cellular plasticity is observed, whereas in the second, cellular heterogeneity is observed. The difference between these terms in relation to Tregs is rather blurred. Considering the promising perspectives of Tregs in regenerative cell-based therapy, the existing confusing data on Treg phenotypes require further investigation and analysis. In our review, we introduce criteria that allow us to distinguish between the heterogeneity and plasticity of Tregs normally and pathologically, taking a closer look at their diversity and drawing the line between two terms. Full article
(This article belongs to the Special Issue Regulatory T Cells and Autoimmunity)
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