Objective Transforming growth factor-β is considered to play a key role in the process of fibrosis in systemic sclerosis (SSc) and in the development of regulatory T cells (Treg) and pro-inflammatory Th17 T cells producing interleukin 17 (IL-17) and IL-22. The authors therefore postulated that SSc could be characterised by a marked Treg/Th17 imbalance. Previous works did not distinguish between the different subsets of Treg and the non-regulatory FoxP3+ cells leading to inconsistent results.
Methods Combined phenotypic and functional analysis of Th17 cells and FoxP3+CD4 T cells, discriminating activated Tregs and resting Tregs from non-regulatory FoxP3+ T cells, in blood and skin of SSc patients.
Results In early disease stages, there is a decreased proportion of activated Tregs. A concomitant resting Treg deficit becomes more apparent with disease progression. Active and diffuse forms of the disease are characterised by a relatively higher proportion of all FoxP3+ subsets, including non-regulatory T cells. No peripheral or local IL-17 amplification was observed. However, the authors found significantly increased IL-22 transcription levels in SSc lesional skin, as compared with healthy skin. Cytofluorometry confirmed the existence in SSc patients and controls of a distinct subset of T cells producing IL-22 in the absence of IL-17.
Conclusion SSc pathogenesis does not appear to be linked to IL-17-, but rather to IL-22-producing cells with skin-homing potential and a concomitant quantitative Treg defect. Active and diffuse forms of the disease are associated with a FoxP3 signature. Altogether, our data depict a status of regulatory/pro-inflammatory T cell imbalance in SSc.
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AM, CP and KD contributed equally to this work as first authors. ST and LA contributed equally to this work as second authors.
Funding This study was supported by Assistance Publique-Hôpitaux de Paris (CIB Pitié-Salpêtrière) and by the Institut National de la Santé et de la Recherche Médicale. M Larsen was supported by the European FP6 ‘ATTACK’ programme (contract: LSHC-CT-2005-018914) and S Trad by the Association pour la Recherche sur le Cancer.
Competing interests None.
Patient consent Obtained.
Ethics approval Approval provided by the local ethics committee of the Pitié-Salpêtrière hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
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