TH17 cells expressing CD146 are significantly increased in patients with Systemic sclerosis

Published on Nov 27, 2019in Scientific Reports4.38
路 DOI :10.1038/S41598-019-54132-Y
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Abstract
Systemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage, excessive fibrosis and abnormal T cells immune-regulation. CD146 is an adhesion molecule essentially expressed in the vascular system, but also on TH17 lymphocytes. In view of the recently described role of CD146 in SSc, we hypothesized an involvement of CD146 positive TH17 cells in this disease. Compared to healthy controls, we showed that both soluble form of CD146 (sCD146), and IL17A levels were increased in patients with SSc with a positive correlation between both factors. A significant increase in TH17 cells attested by an increase of ROR纬T, IL17A mRNA and CD4+ IL17A+ cell was observed in patients with SSc. Interestingly, the percentage of TH17 cells expressing CD146 was higher in patients with SSc and inversely correlated with pulmonary fibrosis. In vitro experiments showed an augmentation of the percentage of TH17 cells expressing CD146 after cell treatment with sCD146, suggesting that, in patients the increase of this sub-population could be the consequence of the sCD146 increase in serum. In conclusion, TH17 cells expressing CD146 could represent a new component of the adaptive immune response, opening the way for the generation of new tools for the management of SSc.
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References25
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#1Haiyan ChuH-Index: 2
#2Shuai Jiang (Fudan University)H-Index: 20
Last. Jiucun Wang (Fudan University)H-Index: 34
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Pulmonary fibrosis is the leading cause of death in systemic sclerosis (SSc). Sirtuin1 (SIRT1) is a deacetylase with known antiinflammatory and antifibrotic activity in the liver, kidney, and skin. The role of SIRT1 in SSc-related pulmonary fibrosis is unknown. In the present work, we determined that the expression of SIRT1 in peripheral blood mononuclear cells of patients with SSc with pulmonary fibrosis is lower than that in patients with SSc without pulmonary fibrosis. In in vivo studies of b...
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#1Paul Balanescu (UMFCD: Carol Davila University of Medicine and Pharmacy)H-Index: 9
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: T cells (especially T helper cells) seem to be strongly associated with systemic sclerosis pathogenesis. Th17-IL-17 axis was proved to be involved in the pathogenesis of multiple autoimmune diseases. By performing a comprehensive research of the literature indexed in PubMed database, the current review summarizes current knowledge related to Th17 and IL-17 in systemic sclerosis. While there is promising data suggesting inhibition of Tregulatory and Th1 signals on one hand and promotion of Th17...
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We highlight for the first time that CD146/sCD146 is involved in fibrotic process during SSc. sCD146 could thus constitute a new biomarker to assess disease activity, and potentially a new target for therapeutic applications.
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#1Glenda Castro (Janssen Pharmaceutica)H-Index: 7
#2Xuejun Liu (Janssen Pharmaceutica)H-Index: 70
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: ROR纬t and ROR伪 are transcription factors of the RAR-related orphan nuclear receptor (ROR) family. They are expressed in Th17 cells and have been suggested to play a role in Th17 differentiation. Although ROR纬t signature genes have been characterized in mouse Th17 cells, detailed information on its transcriptional control in human Th17 cells is limited and even less is known about ROR伪 signature genes which have not been reported in either human or mouse T cells. In this study, global gene expr...
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#1Nilesh Amatya (University of Pittsburgh)H-Index: 8
#2Abhishek V. Garg (University of Pittsburgh)H-Index: 15
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Interleukin (IL)-17 is the founding member of a novel family of inflammatory cytokines. While the proinflammatory properties of IL-17 are key to its host-protective capacity, unrestrained IL-17 signaling is associated with immunopathology, autoimmune disease, and cancer progression. In this review we discuss both the activators and the inhibitors of IL-17 signal transduction, and also the physiological implications of these events. We highlight the surprisingly diverse means by which these regul...
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#1Wenjie Zhao (Ha Tai: Xiamen University)H-Index: 4
#2Xiaoyang YueH-Index: 6
Last. Xinhua Yu (Ha Tai: Xiamen University)H-Index: 20
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Pulmonary fibrosis (PF) is one of the leading causes of death in systemic sclerosis (SSc) patients. Although all SSc patients are characterized by autoimmunity, only part of them suffer from PF, suggesting that beside autoimmunity, some additional factors are involved in the initiation of PF in SSc. In this study, we aimed to identify genetic polymorphisms associated with the status of PF in SSc. We performed that an exhaustive search of the PubMed database was performed to identify eligible stu...
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#1Tomoko Ito (Juntendo University)H-Index: 1
#2Naoto Tamura (Juntendo University)H-Index: 23
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CD146, a transmembrane glycoprotein member of the immunoglobulin superfamily, acts as an adhesion molecule that helps maintain the cell monolayer. Human endothelial cells expressing CD146 are involved in angiogenesis and inflammation. Recently, we developed a sandwich ELISA for detecting soluble CD146 (sCD146) in human serum specimens. The aim of this study is to determine serum levels of sCD146 in patients with systemic sclerosis (SSc) and to examine the relationship between sCD146 levels and c...
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#1Changxin Wu (University of Cambridge)H-Index: 11
#2Jane C. Goodall (University of Cambridge)H-Index: 30
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Expression of the adhesion molecule, CD146/MCAM/MelCAM, on T cells has been associated with recent activation, memory subsets and T helper type 17 (Th17) effector function, and is elevated in inflammatory arthritis. Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA) and spondyloarthritides (SpA). Here, we compared the expression of CD146 on CD4+ T cells between healthy donors (HD) and patients with RA and SpA [ankylosing spondylitis (AS) or psoriatic arthritis (PsA)...
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#1Yan Zhou (Xi'an Jiaotong University)H-Index: 10
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Abstract Objective The objective was to survey the expression and localization of Th17-related cytokines and their correlation with skin lesion severity in early systemic sclerosis (SSc). Methods The mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) from 21 SSc patients and 12 healthy controls (HC). The protein expression was examined by immunohistochemistry (IHC) and Western blotting. Results The RT-qPCR analysis showed a significantly higher expression ...
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Th17 and IL-17 play important roles in the clearance of extracellular bacterial and fungal infections. However, strong evidence also implicates the Th17 lineage in several autoimmune disorders including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. The Th17 subset has also been connected with type I diabetes, although whether it plays a role in the pathogenicity of or protection from the disease remains a controversial ...
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Background & AimsNecroptosis facilitates cell death in a controlled manner and is employed by many cell types following injury. It plays a major role in various liver diseases, albeit the cell type-specific regulation of necroptosis in the liver and especially hepatocytes has not yet been conceptualized. Approaches & ResultsHere, we demonstrate that DNA methylation suppresses RIPK3 expression in human hepatocytes and HepG2 cells. In diseases leading to cholestasis the RIPK3 expression is induced...
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