Expression of TGFβ1 and Its Signaling Components by Peripheral Lymphocytes in Systemic Lupus Erythematosus

Kohut, Eszter; Hajdú, Melinda; Gergely, P; Gopcsa, László; Kilián, K.; Pálóczi, Katalin; Kopper, László; Sebestyén, Anna

doi:10.1007/s12253-008-9119-8

Cited by 14 publications

(10 citation statements)

References 26 publications

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“…Our study found that TGF-β induced generation of CD4 + CD25 high FoxP3 + T cells in HCs, whereas this was not seen in SLE patients. This finding is consistent with a previous study that demonstrated defective expression of TGF-β signal transduction molecules in most SLE patients [40]. Interestingly, we found that the addition of CD200Fc rescued the defective generation of CD4 + CD25 high FoxP3 + T cells in SLE patients, indicating that CD200 could intervene in the TGF-β signaling pathway and promote Treg generation.…”

Section: Discussionsupporting

confidence: 93%

Aberrant CD200/CD200R1 expression and function in systemic lupus erythematosus contributes to abnormal T-cell responsiveness and dendritic cell activity

Tong

et al. 2012

Arthritis Res Ther

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IntroductionCD200 is a type I transmembrane glycoprotein that can regulate the activation threshold of inflammatory immune responses, polarize cytokine production, and maintain immune homeostasis. We therefore evaluated the functional status of CD200/CD200 receptor 1 (CD200R1) interactions in subjects with systemic lupus erythematosus (SLE).MethodsSerum CD200 level was detected by ELISA. The expression of CD200/CD200R1 by CD4+ T cells and dendritic cells (DCs) was examined by flow cytometry, and then compared between SLE patients and healthy controls. Peripheral blood mononuclear cells were stained with carboxyfluorescein diacetate succinimidyl ester and annexin V/propidium iodide for evaluation of the effect of CD200 on cell proliferation and apoptosis. In addition, the effect of CD200 on DC function was determined by transwell migration assay as well as by measurement of binding and phagocytosis of apoptotic cells.ResultsIn SLE patients, the number of CD200+ cells and the level of soluble CD200 were significantly higher than in healthy controls, whereas the expression of CD200R1 by CD4+ T cells and DCs was decreased. Furthermore, the increased CD200 expression by early apoptotic cells contributed to their diminished binding and phagocytosis by DCs in SLE. Importantly, the engagement of CD200 receptor on CD4+ T cells with CD200-Fc fusion protein in vitro reduced the differentiation of T-helper type 17 cells and reversed the defective induction of CD4+CD25highFoxP3+ T cells by transforming growth factor beta in SLE patients. Conversely, blockade of CD200-CD200R1 interaction with anti-CD200R1 antibody promoted CD4+ T-cell proliferation.ConclusionCD200 and CD200R1 expression and function are abnormal in SLE and may contribute to the immunologic abnormalities in SLE.

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Section: Discussionsupporting

confidence: 93%

Aberrant CD200/CD200R1 expression and function in systemic lupus erythematosus contributes to abnormal T-cell responsiveness and dendritic cell activity

Tong

et al. 2012

Arthritis Res Ther

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“…TGF␤1 is mainly expressed in association with membrane vesicles (41), including vesicular structures of higher density than exosomes (42). Although a relative deficiency of TGF␤1 was previously demonstrated in T lymphocytes from SLE patients, circulating levels were increased (43). Such an increase has not been consistently demonstrated (44).…”

Section: Discussionmentioning

confidence: 93%

Unique Protein Signature of Circulating Microparticles in Systemic Lupus Erythematosus

Østergaard

Nielsen

Iversen

et al. 2013

Arthritis & Rheumatism

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Objective. To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases.Methods. Using differential centrifugation and high-sensitivity nano-liquid chromatography tandem mass spectrometry, we systematically profiled proteins of microparticles (MPs) from SLE patients (n ‫؍‬ 12), systemic sclerosis (SSc) patients (n ‫؍‬ 6), and rheumatoid arthritis (RA) patients (n ‫؍‬ 6), as well as healthy controls (n ‫؍‬ 12).Results. We identified 531 unique proteins and showed that the differences between healthy controls and patients with SLE with regard to the abundance of 248 proteins were highly statistically significant. Almost half of the proteins that were increased by >2-fold were complement proteins and Ig (increased by 100-4,000 times). MP Ig and complement loads also distinguished SLE from RA and SSc and correlated strongly with clinical SLE severity. Subsets of microtubule proteins, fibronectin, 14-3-3, and desmosomal proteins as well as ficolin 2 and galectin 3 binding protein were also highly increased. In SLE MPs, levels of cytoskeletal, mitochondrial, and organelle proteins, including lysosome-associated membrane protein 1 and transforming growth factor ␤1, were decreased.Conclusion. The data show that SLE patients have increased numbers of MPs that are heavily tagged for removal and fewer MPs with normal protein composition. SLE MPs are unique and specific proteins that represent novel leads for our understanding of SLE and for the development of new treatments of the disease.

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“…TGF-b is a fibrotic cytokine involved in wound healing, angiogenesis and formation of scar tissue. Plasma levels of TGF-b were significantly elevated in both inactive and active SLE patients compared with controls; however, TGF-mRNA from SLE lymphocytes was greatly reduced or absent [133]. A study evaluating microparticle proteins found that TGF-b was reduced in SLE, which the authors surmise is related to reduction of platelets, a key producer of TGF-b [134].…”

Section: Tgf-mentioning

confidence: 99%

Systemic lupus erythematosus biomarkers: the challenging quest

et al. 2016

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SLE, a multisystem heterogeneous disease, is characterized by production of antibodies to cellular components, with activation of both the innate and the adaptive immune system. Decades of investigation of blood biomarkers has resulted in incremental improvements in the understanding of SLE. Owing to the heterogeneity of immune dysregulation, no single biomarker has emerged as a surrogate for disease activity or prediction of disease. Beyond identification of surrogate biomarkers, a multitude of clinical trials have sought to inhibit elevated SLE biomarkers for therapeutic benefit. Armed with new -omics technologies, the necessary yet daunting quest to identify better surrogate biomarkers and successful therapeutics for SLE continues with tenacity.

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Expression of TGFβ1 and Its Signaling Components by Peripheral Lymphocytes in Systemic Lupus Erythematosus

Cited by 14 publications

References 26 publications

Aberrant CD200/CD200R1 expression and function in systemic lupus erythematosus contributes to abnormal T-cell responsiveness and dendritic cell activity

Aberrant CD200/CD200R1 expression and function in systemic lupus erythematosus contributes to abnormal T-cell responsiveness and dendritic cell activity

Unique Protein Signature of Circulating Microparticles in Systemic Lupus Erythematosus

Systemic lupus erythematosus biomarkers: the challenging quest

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