Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus

Tsai, Yi-Giien; Liao, Pei-Fen; Hsiao, Kai-Hung; Wu, Hung-Ming; Lin, Ching-Yuang; Yang, Kuender D.

doi:10.3389/fimmu.2023.1230264

Cited by 10 publications

(4 citation statements)

References 127 publications

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“…Further studies revealed that in lupus nephritis patients, IL-17 was correlated with the SLE disease activity index (SLEDAI) [48][49] . A higher rate of Treg apoptosis was correlated with SLE severity, suggesting that CD4+ Treg cell abnormalities also affect immune tolerance in SLE patients [50] . It has been established that IL-2 levels and the IL-2/STAT5 signaling pathway control the quantity and functionality of CD4+ Tregs [51] .…”

Section: T Cells and T Cell Co-stimulator Blockersmentioning

confidence: 99%

Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation

Chasov,

Zmievskaya,

Ganeeva

et al. 2024

J Biomed Res

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Systemic lupus erythematosus (SLE) is characterized by a systemic dysfunction of the innate and adaptive immune systems, leading to an attack on healthy tissues of the body. During the development of SLE, pathogenic features, such as the formation of autoantibodies to self-nuclear antigens, caused tissue damage including necrosis and fibrosis, with an increased expression of type Ⅰ interferon (IFN) regulated genes. Treatment of lupus with immunosuppressants and glucocorticoids, which are used as the standard therapy, is not effective enough and causes side effects. As an alternative, more effective immunotherapies have been developed, including monoclonal and bispecific antibodies that target B cells, T cells, co-stimulatory molecules, cytokines or their receptors, and signaling molecules. Encouraging results have been observed in clinical trials with some of these therapies. Furthermore, a chimeric antigen receptor T cells (CAR-T) therapy has emerged as the most effective, safe, and promising treatment option for SLE, as demonstrated by successful pilot studies. Additionally, emerging evidence suggests that gut microbiota dysbiosis may play a significant role in the severity of SLE, and the use of methods to normalize the gut microbiota, particularly fecal microbiota transplantation (FMT), opens up new opportunities for effective treatment of SLE.

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Section: T Cells and T Cell Co-stimulator Blockersmentioning

confidence: 99%

Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation

Chasov,

Zmievskaya,

Ganeeva

et al. 2024

J Biomed Res

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“…Immune tolerance was also influenced by CD4+ Treg cell abnormalities in SLE patients, where an increased rate of Treg apoptosis was correlated with disease severity [55]. The IL-2/STAT5 signaling pathway and IL-2 level was shown to regulate the number and function of CD4+ Treg cells [56]. In mice and SLE patients, treatment with low-dose recombinant IL-2 was found to promote Treg cell-mediated beneficial activities in disease manifestations and to raise the circulating Tfr/Tfh ratio, which was associated with increased renal damage and reduced anti-dsDNA titers.…”

Section: Systemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

Immunotherapy Strategy for Systemic Autoimmune Diseases: Betting on CAR-T Cells and Antibodies

Chasov,

Zmievskaya,

Ganeeva

et al. 2024

Antibodies

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Systemic autoimmune diseases (SAIDs), such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA), are fully related to the unregulated innate and adaptive immune systems involved in their pathogenesis. They have similar pathogenic characteristics, including the interferon signature, loss of tolerance to self-nuclear antigens, and enhanced tissue damage like necrosis and fibrosis. Glucocorticoids and immunosuppressants, which have limited specificity and are prone to tolerance, are used as the first-line therapy. A plethora of novel immunotherapies have been developed, including monoclonal and bispecific antibodies, and other biological agents to target cellular and soluble factors involved in disease pathogenesis, such as B cells, co-stimulatory molecules, cytokines or their receptors, and signaling molecules. Many of these have shown encouraging results in clinical trials. CAR-T cell therapy is considered the most promising technique for curing autoimmune diseases, with recent successes in the treatment of SLE and SSc. Here, we overview novel therapeutic approaches based on CAR-T cells and antibodies for targeting systemic autoimmune diseases.

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“…By inhibiting the activity of Teffs, Tregs help to maintain immune tolerance and prevent excessive or inappropriate immune responses. 13 Tregs that have higher amounts of IL-2R alpha (also called CD25) can bind IL-2 better. This takes IL-2 away from activated Teffs, which are immune cells that fight infection.…”

Section: Immunosuppression and Its Impacts On Pathology And Cancermentioning

confidence: 99%

“…IL-35 acts to suppress the immune response of Teffs, which play a role in the adaptive immune response. By inhibiting the activity of Teffs, Tregs help to maintain immune tolerance and prevent excessive or inappropriate immune responses . Tregs that have higher amounts of IL-2R alpha (also called CD25) can bind IL-2 better.…”

Section: Mechanisms Of Treg-mediated Immunosuppression and Its Impact...mentioning

confidence: 99%

Deciphering Regulatory T-Cell Dynamics in Cancer Immunotherapy: Mechanisms, Implications, and Therapeutic Innovations

Bhattacharya,

Paraskar,

Jha

et al. 2024

ACS Pharmacol. Transl. Sci.

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This Review explores how tumor-associated regulatory cells (Tregs) affect cancer immunotherapy. It shows how Tregs play a role in keeping the immune system in check, how cancers grow, and how well immunotherapy work. Tregs use many ways to suppress the immune system, and these ways are affected by the tumor microenvironment (TME). New approaches to cancer therapy are showing promise, such as targeting Treg checkpoint receptors precisely and using Fc-engineered antibodies. It is important to tailor treatments to each patient's TME in order to provide personalized care. Understanding Treg biology is essential for creating effective cancer treatments and improving the long-term outcomes of immunotherapy.

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Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus

Cited by 10 publications

References 127 publications

Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation

Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation

Immunotherapy Strategy for Systemic Autoimmune Diseases: Betting on CAR-T Cells and Antibodies

Deciphering Regulatory T-Cell Dynamics in Cancer Immunotherapy: Mechanisms, Implications, and Therapeutic Innovations

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