The Immune Pathogenesis of Scleroderma: Context Is Everything
The fundamental mechanisms that drive the pathogenesis of systemic sclerosis (SSc) remain elusive, despite over 50 years of investigation. Here, we review recent progress in the understanding of the immunopathogenesis of SSc. In particular, we consider interleukin-13 (IL13), and its upstream and downstream pathways, as an example of an immune system-derived mediator involved in fibrotic and vascular pathology. Emerging results linking pattern-recognition receptors and interferon pathways to SSc are also stressed. We discuss genetic data linking the immune system to SSc risk and efforts to apply animal models to subsets of patients recently resolved by gene expression profiling. These developments will help build a context for better understanding of previous observations and design of the next generation of studies that may eventually lead to effective treatment.
KeywordsScleroderma Systemic sclerosis Animal models Interleukin-13 Interleukin-33 Toll-like receptor 3 Interferon Immune Pathogenesis
Dr Aliprantis is supported by grants from the Burroughs Wellcome Fund and the National Institutes of Health (K08 AR 054859 and R01 AR060363). Dr Aliprantis’ work relevant to SSc was previously supported by the Scleroderma Research Foundation and Sanofi pharmaceuticals. The authors thank Drs Julia Charles, Susan Ritter, and Joerg Ermann for their thoughtful review and discussion of this manuscript.
No potential conflicts of interest relevant to this article were reported.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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