The Immunobiology of Systemic Sclerosis

Gu, Y. Stephanie; Kong, James; Cheema, Gurtej S.; Keen, Carl L.; Wick, Georg; Gershwin, M. Eric

doi:10.1016/j.semarthrit.2007.10.010

Cited by 143 publications

(133 citation statements)

References 243 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…The disease duration was calculated from the time of onset of the first non-Raynaud phenomenon. Skin sclerosis was evaluated with the modified Rodnan skin thickness score (MRSS) (19) and graded as mild (MRSS, [1][2][3][4][5][6][7][8][9][10][11][12][13][14] or moderateto-severe (MRSS, 15-39) (20). SSc-related interstitial lung disease (ILD) was classified as extensive or limited disease based on combined evaluation with chest high-resolution computed tomography (HRCT) and pulmonary functional tests (21).…”

Section: Patientsmentioning

confidence: 99%

“…S ystemic sclerosis (SSc) is an autoimmune disease characterized by vascular damage, inflammation, immune dysfunction, and fibrosis of the skin and internal organs (1)(2)(3). Endothelial vascular damage is an early event in SSc (1,4) and leads to activation of the immune response with release of various cytokines, autoantibody production, fibroblast activation, and enhanced collagen synthesis (5).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Increased CD226 Expression on CD8+ T Cells Is Associated with Upregulated Cytokine Production and Endothelial Cell Injury in Patients with Systemic Sclerosis

Ayano

Tsukamoto

Kohno

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular damage and fibrosis of the skin and internal organs. Because activated and oligoclonally expanded CD8+ T cells can be detected in peripheral blood and lungs of SSc patients, effector memory CD8+ T cells may play a critical role for organ involvement in SSc; however, the pathogenic functions of effector memory CD8+ T cells remain incompletely understood. In this study, we performed DNA microarray analysis of the sort-purified effector memory CD8+ T cells from SSc patients and healthy controls, and showed that the expression of genes related to immune response and cell adhesion, including CD226 (also known as DNAX accessory molecule-1 [DNAM-1]), was significantly altered. Moreover, detailed analysis of CD226 revealed that CD226highCD8+ T cells were increased in SSc patients (mean, 50.7%) compared with healthy controls (32.9%) and were appreciably associated with the severity of skin sclerosis and interstitial lung disease. Furthermore, CD226+CD8+ T cells produced higher amount of various cytokines than CD226− ones, and CD226highCD8+ T cells from SSc patients showed upregulated IL-13 production and positive correlation with the cytotoxic capacity of CD8+ T cells against HUVECs. Finally, the neutralization of CD226 in CD8+ T cells impaired costimulation, cytokine productions, and cytolysis against HUVECs. These findings indicate that upregulated CD226 expression on CD8+ T cells reflects disease severity and is involved in SSc pathogenesis via the production of various cytokines, including profibrotic IL-13 and endothelial cell injury, and that CD226 may be a useful target in the treatment of SSc.

show abstract

Section: Patientsmentioning

confidence: 99%

mentioning

confidence: 99%

Increased CD226 Expression on CD8+ T Cells Is Associated with Upregulated Cytokine Production and Endothelial Cell Injury in Patients with Systemic Sclerosis

Ayano

Tsukamoto

Kohno

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Scleroderma is a chronic inflammatory disease characterized by widespread fibrosis of the skin and internal organs (1)(2)(3). Vasculopathy and immune activations are the main factors in the pathogenesis of scleroderma, although its pathogenesis is not yet fully understood (1)(2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Genistein protects dermal fibrosis in bleomycin-induced experimental scleroderma

et al. 2015

View full text Add to dashboard Cite

Objective: Genistein, a phytoestrogen, has anti-oxidant, anti-inflammatory, and anti-angiogenic properties. The aim of the present study is to evaluate the protective effect of genistein in bleomycin (BLM)-induced dermal fibrosis. Material and Methods:This study involved four groups of Balb/c mice (n=10 per group). Mice in three groups were administered BLM [100 μg/day in 100 μL phosphate-buffered saline (PBS)] subcutaneously for 4 weeks; the remaining (control) group received only 100 μL/ day of PBS subcutaneously. PBS or BLM was injected into the shaved upper back. Two of the BLM-treated groups also received genistein (1 or 3 mg/kg/day, subcutaneously, to the dorsal front of neck). At the end of the fourth week, all mice were sacrificed and blood and tissue samples were obtained.

show abstract

“…ing interleukin (IL)-4 and transforming growth factor (TGF)-β1 [1][2][3]. Activated fibroblasts (myofibroblasts), which are the key effectors of extracellular matrix (ECM) production, also express pro-fibrotic cytokines and growth factors, including IL-6, TGF-β1, platelet-derived growth factor, and connective tissue growth factor [1][2][3].…”

mentioning

confidence: 99%

“…Activated fibroblasts (myofibroblasts), which are the key effectors of extracellular matrix (ECM) production, also express pro-fibrotic cytokines and growth factors, including IL-6, TGF-β1, platelet-derived growth factor, and connective tissue growth factor [1][2][3]. Therefore, activated fibroblasts show autocrine behavior and require no exogenous stimuli for persistence in their activation [1][2][3]. In addition to the autonomy of fibroblasts, transformation of the non-fibroblastic cells to fibroblastic cells is the other possible pathogenic way leading to scleroderma.…”

mentioning

confidence: 99%

The Protective Effects of Bevacizumab in Bleomycin-Induced Experimental Scleroderma

et al. 2016

View full text Add to dashboard Cite

The Immunobiology of Systemic Sclerosis

Cited by 143 publications

References 243 publications

Increased CD226 Expression on CD8+ T Cells Is Associated with Upregulated Cytokine Production and Endothelial Cell Injury in Patients with Systemic Sclerosis

Increased CD226 Expression on CD8+ T Cells Is Associated with Upregulated Cytokine Production and Endothelial Cell Injury in Patients with Systemic Sclerosis

Genistein protects dermal fibrosis in bleomycin-induced experimental scleroderma

The Protective Effects of Bevacizumab in Bleomycin-Induced Experimental Scleroderma

Contact Info

Product

Resources

About