TY - JOUR T1 - Activated and resting regulatory T cell exhaustion concurs with high levels of interleukin-22 expression in systemic sclerosis lesions JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 1227 LP - 1234 DO - 10.1136/annrheumdis-2011-200709 VL - 71 IS - 7 AU - Alexis Mathian AU - Christophe Parizot AU - Karim Dorgham AU - Salim Trad AU - Laurent Arnaud AU - Martin Larsen AU - Makoto Miyara AU - Miguel Hié AU - Jean-Charles Piette AU - Camille Frances AU - Hans Yssel AU - Zahir Amoura AU - Guy Gorochov Y1 - 2012/07/01 UR - http://ard.bmj.com/content/71/7/1227.abstract N2 - 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. ER -