Regulatory T cells: the future of autoimmune disease treatment

Ryba-Stanisławowska, Monika; Sakowska, Justyna; Zieliński, Maciej; Ławrynowicz, Urszula; Trzonkowski, Piotr

doi:10.1080/1744666x.2019.1620602

Cited by 29 publications

(20 citation statements)

References 178 publications

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“…To date, numerous polyclonal Treg-based clinical trials have been performed in patients with different autoimmune diseases that exhibit promising effects on modulating immune responses. Further investigations are required and underway as the clinical trials NCT02428309, NCT03011021 and, NCT03239470 can verify the therapeutic efficacy of Tregs in autoimmunity ( 6 ) ( Table 3 ).…”

Section: Role In Autoimmunitymentioning

confidence: 99%

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The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

et al. 2021

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Regulatory T cells (Tregs) are an immunosuppressive subgroup of CD4+ T cells which are identified by the expression of forkhead box protein P3 (Foxp3). The modulation capacity of these immune cells holds an important role in both transplantation and the development of autoimmune diseases. These cells are the main mediators of self-tolerance and are essential for avoiding excessive immune reactions. Tregs play a key role in the induction of peripheral tolerance that can prevent autoimmunity, by protecting self-reactive lymphocytes from the immune reaction. In contrast to autoimmune responses, tumor cells exploit Tregs in order to prevent immune cell recognition and anti-tumor immune response during the carcinogenesis process. Recently, numerous studies have focused on unraveling the biological functions and principles of Tregs and their primary suppressive mechanisms. Due to the promising and outstanding results, Tregs have been widely investigated as an alternative tool in preventing graft rejection and treating autoimmune diseases. On the other hand, targeting Tregs for the purpose of improving cancer immunotherapy is being intensively evaluated as a desirable and effective method. The purpose of this review is to point out the characteristic function and therapeutic potential of Tregs in regulatory immune mechanisms in transplantation tolerance, autoimmune diseases, cancer therapy, and also to discuss that how the manipulation of these mechanisms may increase the therapeutic options.

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Section: Role In Autoimmunitymentioning

confidence: 99%

“…The main etiology of autoimmune diseases is not fully understood; however, failure of immunological tolerance is a common cause of each autoimmune condition ( 5 ). Due to the discovery of involvement of Tregs in these patients ( 6 ), Treg-based cellular therapies are opening the door to new therapeutic options for autoimmunity ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

et al. 2021

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“…A large amount of evidence shows that IMN has a reduced proportion of Treg cells in serum and decreased expression of Foxp3 ( 72 ), as well as impaired activation and inhibition of Treg cells ( 81 ). However, the expression of Treg cells in patients improved by rituximab treatment was significantly up-regulated, and the proportion of Treg cells had a prognostic effect on the treatment of rituximab ( 82 , 83 ).…”

Section: Helper T Cells In Imnmentioning

confidence: 99%

Helper T Cells in Idiopathic Membranous Nephropathy

et al. 2021

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Idiopathic membranous nephropathy (IMN) is an autoimmune disease in which the immune system produces an antibody response to its own antigens due to impaired immune tolerance. Although antibodies are derived from plasma cells differentiated by B cells, the T-B cells also contribute a lot to the immune system. In particular, the subsets of helper T (Th) cells, including the dominant subsets such as Th2, Th17, and follicular helper T (Tfh) cells and the inferior subsets such as regulatory T (Treg) cells, shape the immune imbalance of IMN and promote the incidence and development of autoimmune responses. After reviewing the physiological knowledge of various subpopulations of Th cells and combining the existing studies on Th cells in IMN, the role model of Th cells in IMN was explained in this review. Finally, the existing clinical treatment regimens for IMN were reviewed, and the importance of the therapy for Th cells was highlighted.

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“…In our hands, the therapy with expanded Tregs was successfully administered in type 1 diabetes or graft versus host disease (GvHD) after bone marrow transplantation (9)(10)(11). Until now, mainly polyclonal Tregs have been used in clinical therapies due to the problem in technical expansion of antigen-specific cells (12,13). Only recently, we have developed a technique, which allows for efficient production of bulk quantities of antigen-specific Tregs, which seems to be a promising tool for autoimmune therapies (14).…”

Section: Introductionmentioning

confidence: 99%

Antigenic Challenge Influences Epigenetic Changes in Antigen-Specific T Regulatory Cells

et al. 2021

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BackgroundHuman regulatory T cells (Tregs) are the fundamental component of the immune system imposing immune tolerance via control of effector T cells (Teffs). Ongoing attempts to improve Tregs function have led to the creation of a protocol that produces antigen-specific Tregs, when polyclonal Tregs are stimulated with monocytes loaded with antigens specific for type 1 diabetes. Nevertheless, the efficiency of the suppression exerted by the produced Tregs depended on the antigen with the best results when insulin β chain peptide 9-23 was used. Here, we examined epigenetic modifications, which could influence these functional differences.MethodsThe analysis was pefromed in the sorted specific (SPEC, proliferating) and unspecific (UNSPEC, non-proliferating) subsets of Tregs and Teffs generated by the stimulation with monocytes loaded with either whole insulin (INS) or insulin β chain peptide 9-23 (B:9-23) or polyclonal cells stimulated with anti-CD3/anti-CD28 beads (POLY). A relative expression of crucial Tregs genes was determined by qRT-PCR. The Treg-specific demethylated region (TSDR) in FoxP3 gene methylation levels were assessed by Quantitative Methylation Specific PCR (qMSP). ELISA was used to measure genomic DNA methylation and histone H3 post-translational modifications (PTMs).ResultsTregs SPECB:9-23 was the only subset expressing all assessed genes necessary for regulatory function with the highest level of expression among all analyzed conditions. The methylation of global DNA as well as TSDR were significantly lower in Tregs SPECB:9-23 than in Tregs SPECINS. When compared to Teffs, Tregs were characterized by a relatively lower level of PTMs but it varied in respective Tregs/Teffs pairs. Importantly, whenever the difference in PTM within Tregs/Teffs pair was significant, it was always low in one subset from the pair and high in the other. It was always low in Tregs SPECINS and high in Teffs SPECINS, while it was high in Tregs UNSPECINS and low in Teffs UNSPECINS. There were no differences in Tregs/Teffs SPECB:9-23 pair and the level of modifications was low in Tregs UNSPECB:9-23 and high in Teffs UNSPECB:9-23. The regions of PTMs in which differences were significant overlapped only partially between particular Tregs/Teffs pairs.ConclusionsWhole insulin and insulin β chain peptide 9-23 affected epigenetic changes in CD4+ T cells differently, when presented by monocytes. The peptide preferably favored specific Tregs, while whole insulin activated both Tregs and Teffs.

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Regulatory T cells: the future of autoimmune disease treatment

Cited by 29 publications

References 178 publications

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

Helper T Cells in Idiopathic Membranous Nephropathy

Antigenic Challenge Influences Epigenetic Changes in Antigen-Specific T Regulatory Cells

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