Regulatory T-cell levels in systemic lupus erythematosus patients: a meta-analysis

Zhu, Yaowu; Huang, Yi‐Ge; Ming, Bingxia; Wu, Xiaoqian; Chen, Y; Dong, Lingli

doi:10.1177/0961203319828530

Cited by 28 publications

(19 citation statements)

References 43 publications

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“…Anyway, we observed a significant decrease in the percentage of Tregs in our population. This could reflect the initial steps to tolerance breakdown, as a decrease in the frequency or number of Tregs has been associated with AID, such as SLE (28, 29), systemic sclerosis (25–27) or rheumatoid arthritis (30–32). In AAV patients, unlike other AID, an increased proportion of Tregs has rather been reported (36) but with impaired properties (37).…”

Section: Discussionmentioning

confidence: 99%

T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown

et al. 2019

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Background: Chronic silica exposure can lead to silicosis, complicated or not by autoimmune diseases (AID). The pathophysiology of silica-induced AID remains not fully understood, especially immune mechanisms that may develop in patients without yet established silicosis. We conducted a prospective clinical study to analyze the impact of crystalline silica (CS) on T cell phenotype and regulatory T cells (Tregs) frequency, as well as on auto-antibodies development in non-silicotic workers exposed to CS.Methods: Workers with moderate to high exposure level to CS and aged between 30 and 60 years-old were considered for inclusion. Peripheral blood mononuclear cells were analyzed by flow cytometry. Auto-antibodies were screened in serum by immunofluorescence. Blood from 42 and 45 healthy subjects (HC) was used as control for T cell phenotype and serum analyses, respectively.Results: Among the 63 included workers exposed to CS, 55 had full data available and were analyzed. Ten were exposed to CS for <5 years, 18 for 5–10 years and 27 for more than 10 years. The frequency of Tregs (CD4+CD25+CD127−FoxP3+) was significantly lower in CS exposed workers as compared to HC. We found an increased expression of the activation marker HLA-DR on T cells (CD3+, CD4+, and CD8+) of CS exposed workers as compared to HC. Tregs to activated T cells ratio was also lower in exposed subjects. In the latter, HLA-DR expression level and Tregs frequency were significantly associated with CS exposure duration. Serum autoantibody detection was significantly higher in CS exposed workers as compared to HC. Especially, among workers exposed more than 10 years, antinuclear antibodies and ANCA were detected in 44 and 22% among them, as compared to 5 and 2.5% in HC, respectively.Conclusion: This work shows that CS exposure is associated with a decrease of Tregs frequency, an increase of T cell activation status, and a tolerance breakdown against auto-antigens. These results show that alterations of the T cell compartment can be detected early over the course of CS exposure, preceding silicosis development or AID onset.

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Section: Discussionmentioning

confidence: 99%

T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown

et al. 2019

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“…Tregs, however, have immunosuppressive function and play an important role in the induction and maintenance of self-tolerance. The reduced content and dysfunction of Tregs are closely related to the occurrence and development of SLE (6)(7)(8). Tregs injected into lupus mice can control the inflammatory response and alleviate pathological damage (9).…”

Section: Introductionmentioning

confidence: 99%

T Cell Metabolism: A New Perspective on Th17/Treg Cell Imbalance in Systemic Lupus Erythematosus

2020

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The Th17/T-regulatory (Treg) cell imbalance is involved in the occurrence and development of organ inflammation in systemic lupus erythematosus (SLE). Metabolic pathways can regulate T cell differentiation and function, thus contributing to SLE inflammation. Increasingly, data have shown metabolism influences and reprograms the Th17/Treg cell balance, and the metabolic pattern of T cells is different in SLE. Notably, metabolic characteristics of SLE T cells, such as enhanced glycolysis, lipid synthesis, glutaminolysis, and highly activated mTOR, all favored Th17 differentiation and function, which underlie the Th17/Treg cell imbalance in SLE patients. Targeting metabolic pathways to reverse Th17/Treg imbalance offer a promising method for SLE therapy.

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“…It was reported that the imbalance between Th17 and Treg underlies the pathogenesis of SLE 30 . The ratio of Treg/CD4 + T in peripheral blood from SLE patients was markedly lower than in healthy control, while increased Th17/Treg ratio and Th17/Th1 ratio were found in SLE patients 31,32 . Talaat et al 33 indicated that the production of plasma cytokines of IL‐17, IL‐14 and IL‐6 were upregulated in SLE patients, while the production of TGF‐β was downregulated.…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin IIb improved active chromatin‐induced systemic lupus erythematosus via balancing the percentage of Th17 and Treg cells

Dong

et al. 2020

Clin Exp Pharma Physio

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The pathogenesis of systemic lupus erythematosus (SLE) is closely associated with aberrant immune system. Here, the aim of our study was to explore the regulation of cucurbitacin IIb (CuIIb) to Th17/Treg cells in SLE. Compared with normal mice, the percentage of Treg cells was downregulated in SLE mouse model, and Th17 was upregulated. Meantime, the production of Treg‐related transcription factor (foxp3) in SLE model mouse was reduced, and the production of Th17‐related transcription factor (RORγt) was increased. After treatment with CuIIb, the percentage of Treg cells in SLE mice was partly upregulated, and Th17 cells percentage was downregulated. The expression of foxp3 and RORγt in SLE mice were promoted and inhibited by CuIIb treatment, respectively. SLE‐induced kidney injury also was improved by CuIIb treatment. In vitro, we demonstrated again that CuIIb upregulated the percentage of Treg cells in lymphocytes from SLE mice, and downregulated the percentage of Th17 cells. Highly expressed IL‐6 and IL17, and lowly expressed IL‐10 and TGF‐β in lymphocytes from SLE mice were repressed and facilitated by CuIIb treatment, respectively. Overall, our data proved that CuIIb improved kidney injury in SLE mice through balancing the percentage of Th17 and Treg cells. Our data provided a reliable evidence to support the potential of CuIIb in SLE treatment.

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Regulatory T-cell levels in systemic lupus erythematosus patients: a meta-analysis

Cited by 28 publications

References 43 publications

T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown

T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown

T Cell Metabolism: A New Perspective on Th17/Treg Cell Imbalance in Systemic Lupus Erythematosus

Cucurbitacin IIb improved active chromatin‐induced systemic lupus erythematosus via balancing the percentage of Th17 and Treg cells

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