Abstract
Systemic sclerosis is characterized by extensive fibrosis, microvascular stenosis and autoantibody production. All three characteristics can be accounted for by activation of cells of the immune system. Activation of T cells is antigen-driven and occurs early in the course of the disease, before microscopic evidence of fibrosis. Activated T cells are predominantly of the type 2 T-helper lineage, and produce interleukin-4 and interleukin-13, which induce fibrosis. B cells are also activated early in the course of the disease and, through the production of autoantibodies, cause fibroblasts to adopt a profibrotic phenotype. Macrophages in perivascular infiltrates are activated and produce CC-chemokine ligand 2, transforming growth factor β and platelet derived growth factor, all of which promote fibrosis and fibroproliferation. These new insights have direct impact on the treatment of patients with systemic sclerosis; therapies that target T cells, B cells and their harmful mediators are a logical approach, and preliminary data are promising.
Key Points
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Immune cells are activated early in the course of systemic sclerosis pathogenesis, even before fibrosis has developed
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The activation of T cells is antigen-driven, but the antigen (or antigens) is yet unknown
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Activated T cells are mainly of the type 2 T-helper profile and produce IL-4, which promotes fibrosis and antagonizes the antifibrotic effects of interferon-γ
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B cells promote fibrosis through the production of autoantibodies
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Treatments that target immune cells or their harmful soluble mediators have shown promise, and clinical trials are underway
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Sakkas, L., Chikanza, I. & Platsoucas, C. Mechanisms of Disease: the role of immune cells in the pathogenesis of systemic sclerosis. Nat Rev Rheumatol 2, 679–685 (2006). https://doi.org/10.1038/ncprheum0346
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DOI: https://doi.org/10.1038/ncprheum0346
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