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Mechanisms of Disease: the role of immune cells in the pathogenesis of systemic sclerosis

Nature Clinical Practice Rheumatology volume 2, pages 679–685 (2006)Cite this article

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

  • Immune cells are activated early in the course of systemic sclerosis pathogenesis, even before fibrosis has developed

  • The activation of T cells is antigen-driven, but the antigen (or antigens) is yet unknown

  • 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

  • B cells promote fibrosis through the production of autoantibodies

  • Treatments that target immune cells or their harmful soluble mediators have shown promise, and clinical trials are underway

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Figure 1: Interactions between T cells and fibroblasts in systemic sclerosis
Figure 2: Links between immunologic, vascular and fibrotic aspects of systemic sclerosis pathogenesis
Figure 3: B cells interact with endothelial cells and fibroblasts through antibody production

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Authors and Affiliations

  1. Associate Professor of Medicine and Rheumatology and Head of the Rheumatology Section, Thessaly University School of Medicine, Larisa, Greece

    Lazaros I Sakkas

  2. Adjunct Assistant Professor at Temple University School of Medicine, Philadelphia, PA, USA

    Lazaros I Sakkas

  3. Professor of Medicine and Chairman of the Department of Microbiology and Immunology,

    Ian C Chikanza & Chris D Platsoucas

  4. Bone and Joint Research Unit, Barts

    Ian C Chikanza & Chris D Platsoucas

  5. The Royal London Hospital, Queen Mary's School of Medicine and Dentistry, University of London, London

    Ian C Chikanza & Chris D Platsoucas

  6. Consultant in the Department of Rheumatology, Barts and The Royal London Hospital, London, UK

    Ian C Chikanza & Chris D Platsoucas

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  1. Lazaros I Sakkas
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Correspondence to Lazaros I Sakkas.

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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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