Dataset Information

Targeting Regulatory T Cells to Treat Patients With Systemic Lupus Erythematosus.

ABSTRACT: Regulatory T cells (Tregs) are central in integration and maintenance of immune homeostasis. Since breakdown of self-tolerance is a major culprit in the pathogenesis of systemic lupus erythematosus (SLE), restoration of the immune tolerance through the manipulation of Tregs can be exploited to treat patients with SLE. New information has revealed that Tregs besides their role in suppressing the immune response are important in tissue protection and regeneration. Expansion of Tregs with low-dose IL-2 represents an approach to control the autoimmune response. Moreover, control of Treg metabolism can be exploited to restore or improve their function. Here, we summarize the function and diversity of Tregs and recent strategies to improve their function in patients with SLE.

SUBMITTER: Mizui M

PROVIDER: S-EPMC5932391 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Targeting Regulatory T Cells to Treat Patients With Systemic Lupus Erythematosus.

Mizui Masayuki M Tsokos George C GC

Frontiers in immunology 20180417

Regulatory T cells (Tregs) are central in integration and maintenance of immune homeostasis. Since breakdown of self-tolerance is a major culprit in the pathogenesis of systemic lupus erythematosus (SLE), restoration of the immune tolerance through the manipulation of Tregs can be exploited to treat patients with SLE. New information has revealed that Tregs besides their role in suppressing the immune response are important in tissue protection and regeneration. Expansion of Tregs with low-dose ...[more]

PMID: 29755456

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Project description:BackgroundAccumulating evidence indicates that a deficiency in or dysfunction of regulatory T cells (Tregs) is involved in the pathogenesis of systemic lupus erythematosus (SLE). As different markers have been used to identify Tregs, recent studies on the proportions of Tregs in SLE patients have generated controversial results. To clarify the status of Tregs in such patients, we determined the proportions of Tregs present during development of the disease, with special consideration of controversial cellular markers.MethodsWe identified studies reporting the proportions of Tregs in SLE patients by searching relevant databases through March 2018. Using the PRISMA guidelines, we performed a random effects meta-analysis of the frequencies of Tregs defined in different ways. Inconsistency was evaluated using the I-squared index (I2), and publication bias was assessed by examining funnel plot asymmetry using the Begger and Egger tests.ResultsForty-four studies involving 2779 participants were included in the meta-analysis. No significant difference in the proportions of Tregs was evident between 1772 patients and 1007 controls [-0.191, (-0.552, 0.362), p = 0.613, I2 = 95.7%]. We next conducted subanalyses based on individual definitions of Tregs. When the Treg definition included "FOXP3-positive" cells, the proportions did not differ between SLE patients and controls [-0.042, (-0.548, 0.632), p = 0.889, I2 = 96.6%]; this was the case when Tregs were defined as either "CD25low/-FOXP3+" or "CD25high/+FOXP3+" cells. SLE patients had lower proportions of Tregs that were "single CD25-positive" [-1.428, (-1.982, -0.873), p < 0.001, I2 = 93.4%] and "CD127-negative" [-1.093, (-2.002, -0.183), p = 0.018, I2 = 92.6%] compared to controls. Tregs defined as "CD25bright," "CD25bright/highCD127low/-," and "CD25highCD127low/-FOXP3+" did not differ in proportion between SLE patients and controls.ConclusionsThe Treg proportions varied by the cellular identification method used. The proportions of Tregs that were accurately identified and functionally validated fell among patients with SLE. Stricter definitions of Tregs are necessary when evaluating the status of such patients.

Dataset Information

Targeting Regulatory T Cells to Treat Patients With Systemic Lupus Erythematosus.

Publications

Targeting Regulatory T Cells to Treat Patients With Systemic Lupus Erythematosus.

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