Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune fibrotic disease whose pathogenesis is poorly understood and lacks effective therapies. We undertook quantitative analyses of T cell infiltrates in the skin of 35 untreated patients with early diffuse SSc and here show that CD4+ cytotoxic T cells and CD8+ T cells contribute prominently to these infiltrates. We also observed an accumulation of apoptotic cells in SSc tissues, suggesting that recurring cell death may contribute to tissue damage and remodeling in this fibrotic disease. HLA-DR–expressing endothelial cells were frequent targets of apoptosis in SSc, consistent with the prominent vasculopathy seen in patients with this disease. A circulating effector population of cytotoxic CD4+ T cells, which exhibited signatures of enhanced metabolic activity, was clonally expanded in patients with systemic sclerosis. These data suggest that cytotoxic T cells may induce the apoptotic death of endothelial and other cells in systemic sclerosis. Cell loss driven by immune cells may be followed by overly exuberant tissue repair processes that lead to fibrosis and tissue dysfunction.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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er G Abstract Mesenchymal stromal or stem cells (MSC) possess strong immunomodulatory properties. Due to their impressive potential to differentiate into various cell types they are capable of inducing mechanisms of tissue repair. Experimental data have demonstrated impaired MSC function in several rheumatic diseases in vitro; however, the relevance of these phenomena for the pathogenesis of rheumatic disorders has not been convincingly demonstrated. Nevertheless, allogeneic MSC transplantation (MSCT), and possibly autologous MSCT as well, could prove to be an interesting instrument for the treatment of autoimmune...
Source: Zeitschrift fur Rheumatologie - Category: Rheumatology Authors: Tags: Z Rheumatol Source Type: research
Conclusions The clinical trials discussed here, which include several trials investigating novel therapeutic targets, demonstrate that translational research in pemphigus and pemphigoid is a fast-growing field. We thus expect that several novel treatments will be shortly available for the treatment of pemphigus and pemphigoid patients. Given the high, and thus far unmet, medical need in this field (110), this is highly encouraging and will hopefully improve the quality of life of the affected patients. In addition to the compounds and targets described here, several new targets have been recently identified in preclinical...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Therapeutic Targeting of Fibrotic Epithelial-Mesenchymal Transition–An Outstanding Challenge Attila Fintha1, Ákos Gasparics2, László Rosivall3 and Attila Sebe3,4* 12nd Department of Pathology, Semmelweis University, Budapest, Hungary 21st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary 3Department of Pathophysiology, International Nephrology Research and Training Center, Semmelweis University, Budapest, Hungary 4Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany Back in 1995, a landmark paper was published, which shaped the fi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Qiancheng Deng1, Yangyang Luo1,2, Christopher Chang3, Haijing Wu1, Yan Ding4* and Rong Xiao1* 1Hunan Key Laboratory of Medical Epigenetics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China 2Department of Dermatology, Hunan Children's Hospital, Changsha, China 3Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, United States 4Department of Dermatology, Hainan Provincial Dermatology Disease Hospital, Haikou, China Autoimmune diseases are usually complex and multifactorial, characterized by aberrant produc...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, activation of pDCs and glandular epithelial cells by external or endogenous triggers induce the production of type I IFN through TLRs. Type I IFN will lead to BAFF release and activation of B cells with consequent auto-antibody production. Moreover, type I IFN may directly activate T cells which secrete pro-inflammatory cytokines, thus contributing to induce a pro-inflammatory environment. In this scenario, a feedback loop may be postulated between IFN-α production and immune complex formation which will amplify the effect of activated type I IFN system on onset or perpetuation of SS. Role of Chemokin...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Purpose of review To summarize the current clinical experience in the use of autologous hematopoietic stem cell transplantation (HSCT) in autoimmune disease and to explore the concept of durable remission induction and tissue de-remodeling via restoration of normal niche function and “immune reset." Recent findings Controlled clinical trials in systemic sclerosis, multiple sclerosis, and Crohn's disease as well as extensive uncontrolled trial and registry data have established the unique role of HSCT in selected cases. Although HSCT for multiple sclerosis and systemic sclerosis has recently entered several ...
Source: Current Opinion in Hematology - Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research
ConclusionThis study demonstrates the value of WES for the identification of novel gene variants and pathways that may contribute to scleroderma risk and/or severity. The candidate genes we discovered are potential targets for in‐depth functional studies.
Source: Arthritis and Rheumatism - Category: Rheumatology Authors: Tags: Systemic Sclerosis Source Type: research
Conclusion. This study demonstrates the value of WES for the identification of novel gene variants and pathways that may contribute to scleroderma risk and/or severity. The candidate genes we discovered are potential targets for in‐depth functional studies. This article is protected by copyright. All rights reserved.
Source: Arthritis and Rheumatism - Category: Rheumatology Authors: Tags: Brief Report Source Type: research
For years the concept of a "genetic chimera" -- an individual with two genetically distinct cells lines in his/her body -- has sparked the imagination of writers: from Stephen King to Michael Crichton, from CSI to The Office. The idea that an individual could harbor his/her own twin is creepy and intriguing at the same time. Recent advances in DNA sequencing technology have allowed us to probe much deeper into a person's genome, to the point that today scientists believe that chimerism could be far more common than what we originally thought. Chances are, you could be your own twin. But how surprised would you b...
Source: Science - The Huffington Post - Category: Science Source Type: news
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