Activated and resting regulatory T cell exhaustion concurs with high levels of interleukin-22 expression in systemic sclerosis lesions.
Ann Rheum Dis
; 71(7): 1227-34, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-22696687
ABSTRACT
OBJECTIVE:
Transforming growth factor-ß 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Escleroderma Sistêmico
/
Ativação Linfocitária
/
Interleucinas
/
Linfócitos T Reguladores
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article