ArticlePloS one2013
Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Engineered antigen-specific regulatory T cells for autoimmune skin conditions.Autoimmunity reviews · 2021Pooled it
- Wnt/β-Catenin Signaling Pathway Is Involved in Phenotypic Transformation of Human Skin Fibroblasts Induced by IL-17A.Plastic and reconstructive surgery. Global open · 2026Article
- Comparative single-cell multiplex immunophenotyping of therapy-naive patients with rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus shed light on disease-specific composition of the peripheral immune system.Frontiers in immunology · 2024Article
- Novel therapies and innovation for systemic sclerosis skin ulceration.Best practice & research. Clinical rheumatology · 2022Review
- The Pathophysiological Roles of Regulatory T Cells in the Early Phase of Systemic Sclerosis.Frontiers in immunology · 2022Review
- Tissue Resident Foxp3Frontiers in immunology · 2022Review
- A Mechanistic Insight into the Pathogenic Role of Interleukin 17A in Systemic Autoimmune Diseases.Mediators of inflammation · 2022Review
- Contributions of Immune Cells and Stromal Cells to the Pathogenesis of Systemic Sclerosis: Recent Insights.Frontiers in pharmacology · 2022Review
- Increased expression of the ectoenzyme CD38 in peripheral blood plasmablasts and plasma cells of patients with systemic sclerosis.Frontiers in immunology · 2022Article
- Targeting IL-17alpha to promote anti-PD-1 therapy effect by screening the tumor immune microenvironment in a mouse oral carcinogenesis model.Cancer biomarkers : section A of Disease markers · 2021Article
- Bone Marrow Regulatory T Cells Are a Unique Population, Supported by Niche-Specific Cytokines and Plasmacytoid Dendritic Cells, and Required for Chronic Graft-Versus-Host Disease Control.Frontiers in cell and developmental biology · 2021Article
- Regulatory T Cells: Concept, Classification, Phenotype, and Biological Characteristics.Advances in experimental medicine and biology · 2021Article
- The Many Faces of CD4International journal of molecular sciences · 2020Review
- Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci.Genome medicine · 2020Article
- Gastric Juice Expression of Th-17 and T-Reg Related Cytokines in Scleroderma Esophageal Involvement.Cells · 2020Article
- A unique thymus-derived regulatory T cell subset associated with systemic lupus erythematosus.Arthritis research & therapy · 2020Article
- Regulatory T Cell Plasticity and Stability and Autoimmune Diseases.Clinical reviews in allergy & immunology · 2020Review
- Treg cells in autoimmunity: from identification to Treg-based therapies.Seminars in immunopathology · 2019Review
- Attenuation of murine sclerodermatous models by the selective S1PScientific reports · 2019Article
- CD4Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveImmune imbalance between regulatory T (Treg) and Th17 cells is a characteristic of systemic sclerosis (SSc). The functional heterogeneity among Treg can be elucidated by separating Treg into different subsets based on the expression of FoxP3 and CD45RA. The aim of this study was to investigate the role of Treg subsets in the immune imbalance in naïve SSc.
methodsPeripheral blood mononuclear cells (PBMCs) of 31 SSc patients and 33 healthy controls were analyzed for the expression of CD4, CD25, CD45RA, CTLA-4, FoxP3, and IL-17 using flow cytometry. Treg immunesuppression capacity was measured in co-culture experiments. The expression of FoxP3, CTLA-4, IL-17A, and RORC mRNA was measured by real-time PCR.
resultsThe frequency of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly elevated in patients with SSc (3.62±1.14 vs 1.97±0.75, p<0.001) with diminished immunosuppression capacity. In SSc, the proportion of FoxP3(high)CD45RA(-) activated Treg cells (aTreg) was decreased, the proportion of FoxP3(low)CD45RA(-) T cells was increased, and the proportion of FoxP3(low)CD45RA(+) resting Treg cells (rTreg) was decreased. The immune suppression capacity of aTreg and rTreg was diminished, while FoxP3(low)CD45RA(-) T cells exhibited a lack of suppression capacity. The immune dysfunction of aTreg was accompanied by the abnormal expression of CTLA-4. Th17 cell numbers were elevated in SSc, FoxP3(low)CD45RA(-) T cells produced IL-17, confirming their Th17 potential, which was consistent with the elevated levels of FoxP3(+)IL-17(+) cells in SSc.
conclusionA decrease in aTreg levels, along with functional deficiency, and an increase in the proportion of FoxP3(low)CD45RA(-) T cells, was the reason for the increase in dysfunctional Treg in SSc patients, potentially causing the immune imbalance between Treg and Th17 cells.
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