Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Viewpoint
  • Published:

Possible implication of the effector CD4+ T-cell subpopulation TH17 in the pathogenesis of systemic scleroderma

Nature Clinical Practice Rheumatology volume 3, pages 682–683 (2007)Cite this article

Systemic scleroderma (SSc) is one of the most severe chronic, autoimmune connective tissue diseases of unknown etiology.1 The 10-year survival rate is only 60–88%; this is even lower in specific disease subsets, such as patients with pulmonary fibrosis and pulmonary atrial hypertension.2 The main patho-anatomical feature of SSc is early vasculopathy, often associated with severe and prolonged inflammation, which leads to tissue fibrosis and atrophy. The pathology often starts in the extremities, notably the skin of fingers and toes. Fibrosis can also affect most of the internal organs, and in the most progressive or advanced cases this leads to organ compromise and failure. Although the cellular and molecular links between the disease sequelae remain incompletely understood, the inflammatory process seems to be a primary driver of the pathological mechanisms of disease activity.3

A key feature of the inflammatory lesions found in affected skin is the presence of T cells. These T-cell infiltrates are mainly of the CD4+ memory (CD45RO+) phenotype. Within the CD4+ T-cell population, different functional subsets have been characterized. The CD4+ helper T cells (TH cells) are often divided into the TH1 and TH2 groups based on their different cytokine repertoires and distinct functional activities. Although this differentiation is most pronounced in mice, it has gained attention in humans because it helps to understand and explain a number of fundamental immunological mechanisms. TH1 cells are characterized by interferon (IFN) γ, interleukin (IL)-2 and TNF secretion, whereas TH2 cells produce predominantly IL-4, IL-5, IL-10 and IL-13. Despite extensive studies, it has proved difficult to assign T cells associated with SSc to either functional group, as they do not produce high amounts of cytokines characteristic of either the TH1 or TH2 subsets. Examination of other T-cell cytokines that might provide clues to unravel the links between immunopathy and tissue fibrosis in SSc led Kurasawa et al. to report the presence of high levels of IL-17, especially in the early stages of the disease.4 This study suggested that the T-cell activity in SSc takes place outside the conventional TH1 and TH2 subsets. Although initially difficult to explain within the confines of current thinking, the recent characterization of two new T-cell subpopulations within the CD4+ subset allows the potential role of IL-17 in SSc to be discussed. These two CD4+ T-cell subsets have been named regulatory T cells (Treg) and TH17.5,6

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Varga J and Abraham D (2007) Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest 117: 557–567

    Article  CAS  Google Scholar 

  2. Denton CP et al. (2006) Mechanisms and consequences of fibrosis in systemic sclerosis. Nat Clin Pract Rheumatol 2: 134–144

    Article  Google Scholar 

  3. Sakkas LI and Platsoucas CD (2004) Is systemic sclerosis an antigen-driven T cell disease? Arthritis Rheum 50: 1721–1733

    Article  CAS  Google Scholar 

  4. Kurasawa K et al. (2000) Increased interleukin-17 production in patients with systemic sclerosis. Arthritis Rheum 43: 2455–2463

    Article  CAS  Google Scholar 

  5. Hori S et al. (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057–1061

    Article  CAS  Google Scholar 

  6. Wynn TA (2005) T(H)-17: a giant step from T(H)1 and T(H)2. Nat Immunol 6: 1069–1070

    Article  CAS  Google Scholar 

  7. Doganci A et al. (2005) The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo. J Clin Invest 115: 313–325

    Article  CAS  Google Scholar 

  8. Chen W et al. (2003) Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198: 1875–1886

    Article  CAS  Google Scholar 

  9. Chung Y et al. (2006) Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes. Cell Res 16: 902–907

    Article  CAS  Google Scholar 

  10. Liang SC et al. (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203: 2271–2279

    Article  CAS  Google Scholar 

  11. Maini RN et al. (2006) Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum 54: 2817–2829

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. B Deleuran is Associate Professor in the Department of Rheumatology at Aarhus University Hospital, Denmark,

    Bent Deleuran

  2. DJ Abraham is a Professor of Cell and Molecular Biology at the Centre for Rheumatology, Royal Free and University College Medical School, London.,

    David J Abraham

Authors
  1. Bent Deleuran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David J Abraham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bent Deleuran.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Deleuran, B., Abraham, D. Possible implication of the effector CD4+ T-cell subpopulation TH17 in the pathogenesis of systemic scleroderma. Nat Rev Rheumatol 3, 682–683 (2007). https://doi.org/10.1038/ncprheum0618

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncprheum0618

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing