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Cells
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Regulatory T Cells and Autoimmune Diseases
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Regulatory T Cells and Autoimmune Diseases

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

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 14909

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,

Regulatory T cells (Tregs) are a specialized subset of CD4+ T cells which exert immunosuppressive functions and play essential roles in maintaining immune homeostasis and immune tolerance. Tregs play pivotal roles in the progression and prognosis of diverse diseases. These cells are characterized by the expression of the master transcription factor forkhead box transcription factor (FoxP3) that controls their functions. Dysregulations of the Tregs population compromise the immunosuppressive functions of Tregs against self-tissue components and initiate the progression of numerous autoimmune diseases, including autoimmune thyroid disease (AITD), rheumatoid arthritis (RA), immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX), systemic lupus erythematosus (SLE), multiple sclerosis (MS), type 1 diabetes (T1D), and inflammatory bowel disease (IBD). Thus, the complete understanding of how Tregs possess considerable importance in supervising the immune responses in autoimmune diseases and re-establishing self-tolerance is highly desirable, not just for in-depth insights into the mechanisms underlying Tregs dysfunction in autoimmunity but also for the optimal benefits of Treg-based therapies in autoimmune diseases.

The purpose of this Special Issue is to collect reviews and original studies focusing on the role of Tregs in autoimmune diseases. We especially welcome investigators to address the cellular and molecular factors that influence the CD4+Foxp3+ Treg development, homeostasis, and function, with emphasis on the new knowledge available on the role and function of Tregs, and the updated status of therapeutic strategies in modulating Tregs to understand their functions in autoimmune diseases better.  

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
  • Foxp3
  • cell therapy
  • autoimmune disease
  • immunotherapy
  • inflammation
  • tolerance

Published Papers (4 papers)

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Research

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12 pages, 2238 KiB  
Article
The ADP-Ribosylation Factor 4d Restricts Regulatory T-Cell Induction via Control of IL-2 Availability
by Bernd Geers, Julia Hagenstein, Jessica Endig, Hanna Ulrich, Laura Fleig, Paulina Sprezyna, Julita Mikulec, Lukas Heukamp, Gisa Tiegs and Linda Diehl
Cells 2022, 11(17), 2639; https://doi.org/10.3390/cells11172639 - 25 Aug 2022
Cited by 1 | Viewed by 1522
Abstract
Interleukin-2 is central to the induction and maintenance of both natural (nTreg) and induced Foxp3-expressing regulatory T cells (iTreg). Thus, signals that modulate IL-2 availability may, in turn, also influence Treg homeostasis. Using global knockout and cell-specific knockout [...] Read more.
Interleukin-2 is central to the induction and maintenance of both natural (nTreg) and induced Foxp3-expressing regulatory T cells (iTreg). Thus, signals that modulate IL-2 availability may, in turn, also influence Treg homeostasis. Using global knockout and cell-specific knockout mouse models, we evaluated the role of the small GTPase ADP-ribosylation factor 4d (Arl4d) in regulatory T-cell biology. We show that the expression of Arl4d in T cells restricts both IL-2 production and responsiveness to IL-2, as measured by the phosphorylation of STAT5. Arl4d-deficient CD4 T cells converted more efficiently into Foxp3+ iTreg in vitro in the presence of αCD3ε and TGFβ, which was associated with their enhanced IL-2 secretion. As such, Arl4d−/− CD4 T cells induced significantly less colonic inflammation and lymphocytic infiltration in a model of transfer colitis. Thus, our data reveal a negative regulatory role for Arl4d in CD4 T-cell biology, limiting iTreg conversion via the restriction of IL-2 production, leading to reduced induction of Treg from conventional CD4 T cells. Full article
(This article belongs to the Special Issue Regulatory T Cells and Autoimmune Diseases)
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19 pages, 2754 KiB  
Article
Induced Human Regulatory T Cells Express the Glucagon-like Peptide-1 Receptor
by Anna K. O. Rode, Terkild Brink Buus, Veronika Mraz, Fatima Abdul Hassan Al-Jaberi, Daniel Villalba Lopez, Shayne L. Ford, Stephanie Hennen, Ina Primon Eliasen, Ib Vestergaard Klewe, Leila Gharehdaghi, Adrian Dragan, Mette M. Rosenkilde, Anders Woetmann, Lone Skov, Niels Ødum, Charlotte M. Bonefeld, Martin Kongsbak-Wismann and Carsten Geisler
Cells 2022, 11(16), 2587; https://doi.org/10.3390/cells11162587 - 19 Aug 2022
Cited by 9 | Viewed by 3561
Abstract
The glucagon-like peptide-1 receptor (GLP-1R) plays a key role in metabolism and is an important therapeutic target in diabetes and obesity. Recent studies in experimental animals have shown that certain subsets of T cells express functional GLP-1R, indicating an immune regulatory role of [...] Read more.
The glucagon-like peptide-1 receptor (GLP-1R) plays a key role in metabolism and is an important therapeutic target in diabetes and obesity. Recent studies in experimental animals have shown that certain subsets of T cells express functional GLP-1R, indicating an immune regulatory role of GLP-1. In contrast, less is known about the expression and function of the GLP-1R in human T cells. Here, we provide evidence that activated human T cells express GLP-1R. The expressed GLP-1R was functional, as stimulation with a GLP-1R agonist triggered an increase in intracellular cAMP, which was abrogated by a GLP-1R antagonist. Analysis of CD4+ T cells activated under T helper (Th) 1, Th2, Th17 and regulatory T (Treg) cell differentiation conditions indicated that GLP-1R expression was most pronounced in induced Treg (iTreg) cells. Through multimodal single-cell CITE- and TCR-sequencing, we detected GLP-1R expression in 29–34% of the FoxP3+CD25+CD127- iTreg cells. GLP-1R+ cells showed no difference in their TCR-gene usage nor CDR3 lengths. Finally, we demonstrated the presence of GLP-1R+CD4+ T cells in skin from patients with allergic contact dermatitis. Taken together, the present data demonstrate that T cell activation triggers the expression of functional GLP-1R in human CD4+ T cells. Given the high induction of GLP-1R in human iTreg cells, we hypothesize that GLP-1R+ iTreg cells play a key role in the anti-inflammatory effects ascribed to GLP-1R agonists in humans. Full article
(This article belongs to the Special Issue Regulatory T Cells and Autoimmune Diseases)
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Review

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18 pages, 1291 KiB  
Review
The Regulatory-T-Cell Memory Phenotype: What We Know
by Julia N. Khantakova, Aleksey S. Bulygin and Sergey V. Sennikov
Cells 2022, 11(10), 1687; https://doi.org/10.3390/cells11101687 - 19 May 2022
Cited by 17 | Viewed by 6599
Abstract
In immunology, the discovery of regulatory T (Treg) cells was a major breakthrough. Treg cells play a key role in pregnancy maintenance, in the prevention of autoimmune responses, and in the control of all immune responses, including responses to self cells, cancer, infection, [...] Read more.
In immunology, the discovery of regulatory T (Treg) cells was a major breakthrough. Treg cells play a key role in pregnancy maintenance, in the prevention of autoimmune responses, and in the control of all immune responses, including responses to self cells, cancer, infection, and a transplant. It is currently unclear whether Treg cells are capable of long-term memory of an encounter with an antigen. Although the term “immunological memory” usually means an enhanced ability to protect the body from reinfection, the memory of the suppressive activity of Treg cells helps to avoid the state of generalized immunosuppression that may result from the second activation of the immune system. In this review, we would like to discuss the concept of regulatory memory and in which tissues memory Treg cells can perform their functions. Full article
(This article belongs to the Special Issue Regulatory T Cells and Autoimmune Diseases)
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Other

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9 pages, 2174 KiB  
Brief Report
Regulatory T Cells from Patients with Rheumatoid Arthritis Are Characterized by Reduced Expression of Ikaros Zinc Finger Transcription Factors
by Mara Dittrich-Salamon, Anja Meyer, Shuaifeng Yan, Eva Steinbach-Knödgen, Konstantin Kotschenreuther, David Stahl, Carola tho Pesch, Joanna Schiller, Franziska Byrtus, Dorothee Jochimsen, Viktoria Golumba-Nagy and David M. Kofler
Cells 2022, 11(14), 2171; https://doi.org/10.3390/cells11142171 - 11 Jul 2022
Cited by 2 | Viewed by 2484
Abstract
Regulatory T (Treg) cells play an important role in immune tolerance and contribute to the prevention of autoimmune diseases, including rheumatoid arthritis (RA). The differentiation, function and stability of Treg cells is controlled by members of the Ikaros zinc finger transcription factor family. [...] Read more.
Regulatory T (Treg) cells play an important role in immune tolerance and contribute to the prevention of autoimmune diseases, including rheumatoid arthritis (RA). The differentiation, function and stability of Treg cells is controlled by members of the Ikaros zinc finger transcription factor family. In this study, we aimed to reveal how the expression of Ikaros transcription factors is affected by disease activity in RA. Therefore, we analyzed the ex vivo expression of Ikaros, Helios, Aiolos and Eos in Treg cells, Th17 cells and Th1 cells from RA patients by flow cytometry. We found significantly reduced expression of Helios, Aiolos and Eos in Treg cells from RA patients as compared to healthy controls. Moreover, Helios and Aiolos levels correlated with disease activity, as assessed by DAS28-CRP. In addition, Ikaros, Helios and Aiolos were significantly downregulated in Th1 cells from RA patients, while no difference between healthy individuals and RA was observed in Th17 cells. In summary, Helios and Aiolos expression in Treg cells correlates with disease activity and the expression levels of Ikaros transcription factors are diminished in Treg cells from RA patients. This observation could explain the reduced stability of Treg cells in RA. Full article
(This article belongs to the Special Issue Regulatory T Cells and Autoimmune Diseases)
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