Regulatory T cells in systemic sclerosis

Abstract

In recent years, accumulating evidence suggest that regulatory T cells (Tregs) are of paramount importance for the maintenance of immunological self-tolerance and immune homeostasis, even though they represent only about 5-10% of the peripheral CD4+ T cells in humans. Their key role is indeed supported by the spontaneous development of autoimmune diseases after Tregs depletion in mice. Moreover, there is also a growing literature that investigates possible contribution of Tregs numbers and activity in various autoimmune diseases. The contribution of Tregs in autoimmune disease has opened up a new therapeutic avenue based on restoring a healthy balance between Tregs and effector T-cells, such as Treg-based cellular transfer or low-dose IL-2 modulation. These therapies hold the promise of modulating the immune system without immunosuppression, while several issues regarding efficacy and safety need to be addressed. Systemic sclerosis (SSc) is an orphan connective tissue disease characterized by extensive immune abnormalities but also microvascular injury and fibrosis. Recently, data about the presence and function of Tregs in the pathogenesis of SSc have emerged although they remain scarce so far. First, there is a general agreement in the medical literature with regard to the decreased functional ability of circulating Tregs in SSc. Second the quantification of Tregs in patients have led to contradictory results; although the majority of the studies report reduced frequencies, there are conversely some indications suggesting that in case of disease activity circulating Tregs may increase. This paradoxical situation could be the result of a compensatory, but inefficient, amplification of Tregs in the context of inflammation. Nevertheless, these results must be tempered with regards to the heterogeneity of the studies for the phenotyping of the patients and of the most importance for Tregs definition and activity markers. Therefore, taking into account the appealing developments of Tregs roles in autoimmune diseases, together with preliminary data published in SSc, there is growing interest in deciphering Tregs in SSc, both in humans and mice models, to clarify whether the promises obtained in other autoimmune diseases may also apply to SSc.