Abstract
Systemic sclerosis (SSc), or scleroderma, is characterized by fibrosis of the skin and internal organs, vascular abnormalities and alterations of the immune response compartment. T cells are present in affected tissues, including the skin, early in the disease course, appear to be oligoclonal, indicating an antigen-driven process, and preferentially produce Th2 cytokines, including IL-4 and IL-13, which may directly favor excessive extracellular matrix deposition. Th1 cells may also be present. Initial determinations indicate that Th17 numbers are increased and T cells with regulatory functions are defective. Of interest, genetic association studies have preferentially identified polymorphisms of genes coding for molecules belonging to the immune system as risk factors for SSc development, further stressing the importance of immune dysregulation in SSc pathobiology. While current therapeutic approaches remain disappointing, we discuss the advance in our understanding of the immune abnormalities characteristic of SSc in the perspective of identifying novel therapeutic targets.
Financial & competing interests disclosure
Work supported in part by grant 31003A_124941/1 from the Swiss National Science Foundation to Carlo Chizzolini. Marie-Elise Truchetet is supported by a grant from the University Hospital of Bordeaux, France. Elisa Montanari is supported by a grant from the Manodori Foundation, Reggio Emilia, Italy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.