Foxp3, Regulatory T Cell, and Autoimmune Diseases

Jin, Tao; Cheng, Miao; Tang, Jiang; Liu, Qin; Fan, Ping; Li, Xiang Pei

doi:10.1007/s10753-016-0470-8

Cited by 110 publications

(77 citation statements)

References 140 publications

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“…Defects in the number or function of Tregs led to various autoimmune diseases and graft rejection, including SLE, rheumatoid Arthritis (RA) and graft-versus-host disease (GVHD) [4,6,27,28]. It was reported that patients with a defect in CD4+FoxP3+ Tregs developed lupus nephritis [29] and that the ratio of FoxP3 + / CD3 + cells was significantly reduced in kidney biopsies of patients with lupus nephritis [30].…”

Section: Foxp3mentioning

confidence: 99%

Mangiferin Attenuates Murine Lupus Nephritis by Inducing CD4+Foxp3+ Regulatory T Cells via Suppression of mTOR Signaling

Liang

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Lupus nephritis (LN) is an autoimmune glomerulonephritis that frequently develops secondary to systemic lupus erythematosus. Patients with LN require extensive treatments with global immunosuppressive agents. However, long-term treatment with conventional immunosuppressants may cause various side effects. Therefore, it’s important to seek alternative drugs for treating LN. Here we aimed to investigate the immunoregulatory effects of mangiferin (MG), an ingredient that was originally extracted from natural herbs, including Mangifera Indica Linn. and Rhizoma Anemarrhenae. Methods: FasL-deficient B6/ gld mice were used as a spontaneous LN model. The serum anti-dsDNA Ab and creatinine levels were analyzed via ELISA. Renal histology and immunopathology were determined using H&E and PAS staining, immunofluorescence (IgG and C3), and IHC staining (CD3 and a-SMA). Cytokine gene expression was measured by RT-PCR assays while effector T cells and Tregs were enumerated by flow analysis. Finally, the proliferation and apoptosis of T cells were measured by CFSE staining and flow analysis while their mTOR signaling was detected through Western blotting. Results: We found that administration of MG ameliorated LN in lupus-prone B6/gld mice by reducing the urinary protein and serum creatinine levels, diminishing T cell infiltration in kidneys and improving renal immunopathology. MG also significantly lowered the percentages of CD44^highCD62L^low effector T cells in B6/gld mice. Importantly, treatments with MG augmented CD4⁺FoxP3⁺ Treg frequencies in spleens, lymph nodes and kidneys of B6/gld mice. It also induced CD4⁺FoxP3⁺ Tregs from CD3⁺ T cells in vitro and promoted Treg proliferation. Furthermore, it inhibited CD3⁺ T cell proliferation in vitro and suppressed their phosphorylation of mTOR and its downstream P70S6K. However, MG did not promote T cell apoptosis, implying that it is not cytotoxic. Depletion of CD4⁺CD25⁺FoxP3⁺ Tregs in B6/gld mice abrogated its therapeutic effects on LN. Conclusion: MG exerts a novel therapeutic effect on murine LN via upregulating CD4⁺FoxP3⁺ Tregs, downregulating mTOR/p70S6K pathway and improving renal immunopathology. It may be useful for treating LN in clinic.

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Section: Foxp3mentioning

confidence: 99%

Mangiferin Attenuates Murine Lupus Nephritis by Inducing CD4+Foxp3+ Regulatory T Cells via Suppression of mTOR Signaling

Liang

Zhou

et al. 2018

Cell Physiol Biochem

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“…Our result for FOXP3 rs3761548 polymorphism in grade 4 knee OA patients showed that subjects carrying the C variant allele were at higher risk for knee OA in codominant, dominant and overdominant genetic models. Previous studies have shown that functional FOXP3 variants cause several immune‐related disorders, including RA, systemic lupus erythematosus, autism, multiple sclerosis and preeclampsia, probably by changing FOXP3 expression and/or function . Moreover, FOXP3 rs3761548 AA genotype has been found to be associated with Behcet's disease, RA and spontaneous abortion in a Chinese Han population .…”

Section: Discussionmentioning

confidence: 98%

FOXP3 rs3761548 polymorphism is associated with knee osteoarthritis in a Turkish population

et al. 2018

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“…The main function of Treg is to inhibit the excessive activation of effector T cells and prevent immune damage to the body (Wahren‐Herlenius & Dorner, ). Decreased number and dysfunction of Treg cells are often found in AIDs (Tao et al, ). Among cell surface molecular markers, Treg cell is often defined as CD4 + CD25 + FOXP3 + CD127 low T‐cell subgroup (Dominguez‐Villar & Hafler, ).…”

Section: Introductionmentioning

confidence: 99%

Decreased number and impaired function of type 1 regulatory T cells in autoimmune diseases

Jia

Zhai

Wang

et al. 2019

Journal Cellular Physiology

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Type 1 regulatory T (Tr1) cell is a special type of T regulatory cells with surface molecular markers such as lymphocyte‐activation gene 3 and CD49b. A key property of Tr1 cells is the capability to produce high‐level interleukin 10 (IL‐10) upon activation, in a FOXP3‐independent manner. The immunosuppressive function of IL‐10 producing Tr1 cells has been extensively studied for many years. Autoimmune diseases (AIDs) are conditions in which the immune system breaks down and starts to attack the body. AIDs include inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis (MS), type 1 diabetes mellitus, Greaves' disease, and so forth. In recent years, more and more studies have documented that the number of Tr1 cells is decreased and the function is inhibited in a variety of AIDs, among which MS is the most widely studied. The protocol for engineering Tr1 cell therapy has been established and is gradually being used in clinical practice in recent years. Tr1 cell therapy has been proven to be safe and effective, but it is mainly involved in myeloid leukemia, graft versus host disease currently. Its therapeutic role in AIDs still needs to be further explored. In this study, we will summarize the research advances of Tr1 cells in AIDs, which will provide useful information for treating AIDs through Tr1 cell therapy in the future.

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Foxp3, Regulatory T Cell, and Autoimmune Diseases

Cited by 110 publications

References 140 publications

Mangiferin Attenuates Murine Lupus Nephritis by Inducing CD4+Foxp3+ Regulatory T Cells via Suppression of mTOR Signaling

Mangiferin Attenuates Murine Lupus Nephritis by Inducing CD4+Foxp3+ Regulatory T Cells via Suppression of mTOR Signaling

FOXP3 rs3761548 polymorphism is associated with knee osteoarthritis in a Turkish population

Decreased number and impaired function of type 1 regulatory T cells in autoimmune diseases

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