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Systemic sclerosis (SSc) is an autoimmune connective tissue disease in which there is vascular damage, inflammation and ultimately tissue fibrosis. Among all the autoinflammatory conditions, SSc has the highest all-cause mortality and while substantial progress made in understanding the disease in terms of cellular and molecular details, currently no specific effective therapy exists.
In recent times, it has been elucidated that immune cells play a key role in this disease.1 2 Accumulating evidence suggests activation of various innate immune cells and secretion of various profibrotic cytokines but precisely how this activation of innate cells and activation and transdifferentiation of fibroblasts to myofibroblasts secreting matrix has been opaque. Recently, though a manuscript by Odell et al in Science Immunology has made an important contribution to this area.3
The authors first identified in freshly isolated skin biopsies from healthy controls and patients with early diffuse SSc that the fibroblasts and pericytes from patients with SSc were identified by elevated receptor tyrosine kinase signalling. In particular, the epidermal growth factor receptor (EGFR) and in whole skin biopsies there was elevated phosphorylated EGFR expression, suggestive of activation, as it is known that on activation the receptor is phosphorylated at sites in its cytoplasmic domain. This was demonstrated in both the skin and lung. They then further identified epiregulin as being upregulated in both skin and lung of patients with SSc and that the primary cell type that had the highest expression was dendritic cells, and in particularly the DC3 subset. This is a newly described specific subset of dendritic cells that are distinct from conventional dendritic cells and their development relies on granuloccyte monocyte-colonly stimuating factor (GM-CSF) and appear to be able to prime T cells.4 The epiregulin positive cells had elevated markers of DC3 subtype including FCN1 and VCAN and …
Handling editor Josef S Smolen
Contributors I contributed solely to this work.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Commissioned; externally peer reviewed.