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Front Immunol. 2015 Jun 8;6:272. doi: 10.3389/fimmu.2015.00272. eCollection 2015.

Pathogenesis of Systemic Sclerosis.

Author information

1
Department of Medicine, Division of Connective Tissue Diseases, The University of Tennessee Health Science Center , Memphis, TN , USA ; Department of Veterans Affairs Medical Center , Memphis, TN , USA.
2
Section of Pediatric Rheumatology, Department of Pediatrics, The University of Tennessee Health Science Center , Memphis, TN , USA.
3
Department of Medicine, Division of Connective Tissue Diseases, The University of Tennessee Health Science Center , Memphis, TN , USA.

Abstract

Systemic scleroderma (SSc) is one of the most complex systemic autoimmune diseases. It targets the vasculature, connective tissue-producing cells (namely fibroblasts/myofibroblasts), and components of the innate and adaptive immune systems. Clinical and pathologic manifestations of SSc are the result of: (1) innate/adaptive immune system abnormalities leading to production of autoantibodies and cell-mediated autoimmunity, (2) microvascular endothelial cell/small vessel fibroproliferative vasculopathy, and (3) fibroblast dysfunction generating excessive accumulation of collagen and other matrix components in skin and internal organs. All three of these processes interact and affect each other. The disease is heterogeneous in its clinical presentation that likely reflects different genetic or triggering factor (i.e., infection or environmental toxin) influences on the immune system, vasculature, and connective tissue cells. The roles played by other ubiquitous molecular entities (such as lysophospholipids, endocannabinoids, and their diverse receptors and vitamin D) in influencing the immune system, vasculature, and connective tissue cells are just beginning to be realized and studied and may provide insights into new therapeutic approaches to treat SSc.

KEYWORDS:

adaptive immunity; animal models; fibrosis; innate immunity; scleroderma; systemic sclerosis; vasculopathy

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