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A Unifying Hypothesis for Scleroderma: Identifying a Target Cell for Scleroderma

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Abstract

We propose that a recent change in the conception of the role of type 1 interferon and the identification of adventitial stem cells suggests a unifying hypothesis for scleroderma. This hypothesis begins with vasospasm. Vasospasm is fully reversible unless, as proposed here, the resulting ischemia leads to apoptosis and activation of type 1 interferon. The interferon, we propose, initiates immune amplification, including characteristic scleroderma-specific antibodies. We propose that the interferon also acts on adventitial stem cells, producing myofibroblasts, rarefaction, and intimal hyperplasia—three morphologic changes that characterize this disease. Regulator of G-protein signaling 5 (RGS5), a regulator of vasoactive G-protein–coupled receptors, is a cell type–specific marker of pericytes and scleroderma myofibroblasts. RGS5 may provide a key link between initial hyperplasia and fibrosis in this disease.

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Acknowledgment

Drs. Mahoney, Fleming, and Schwartz have received grant support from the Scleroderma Research Foundation.

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No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Department of Pathology, Center for Cardiovascular Biology, University of Washington School of Medicine, 815 Mercer Street, Seattle, WA, 98109, USA

    William M. Mahoney Jr, Jo Nadine Fleming & Stephen M. Schwartz

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  1. William M. Mahoney Jr
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  2. Jo Nadine Fleming
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  3. Stephen M. Schwartz
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Correspondence to Stephen M. Schwartz.

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Mahoney, W.M., Fleming, J.N. & Schwartz, S.M. A Unifying Hypothesis for Scleroderma: Identifying a Target Cell for Scleroderma. Curr Rheumatol Rep 13, 28–36 (2011). https://doi.org/10.1007/s11926-010-0152-8

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