Activated and resting regulatory T cell exhaustion concurs with high levels of interleukin-22 expression in systemic sclerosis lesions. Issue 7 (13th June 2012)

• Record Type: Journal Article
• Authors: Mathian, Alexis; Parizot, Christophe; Dorgham, Karim; Trad, Salim; Arnaud, Laurent; Larsen, Martin; Miyara, Makoto; Hié, Miguel; Piette, Jean-Charles; Frances, Camille; Yssel, Hans; Amoura, Zahir; Gorochov, Guy
• Is Part Of: Annals of the rheumatic diseases. Volume 71:Issue 7(2012)
• Page Start: 1227
• Page End: 1234
• Publication Date: 2012-06-13
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2011-200709
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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.