T cell abnormalities in systemic sclerosis with a focus on Th17 cells

Systemic sclerosis (SSc) is a connective tissue disorder characterized by vascular alterations and deregulated fibroblast activation leading to fibrosis of the skin and internal organs. SSc is thought to be an autoimmune disease, owning the presence of auto-antibodies. Genetic studies lend support to the critical role exerted by the immune response in the physiopathology of the disease, since several of the SSc-associated polymorphisms have been found in genes involved in the immune response. Oligoclonal T cells, preferentially producing type 2 cytokines, are present in affected tissues and peripheral blood early in the disease course, and their soluble mediators favor the production of pro-fibrotic and pro-angiogenic factors by fibroblasts, most likely participating in the establishment of fibrosis. More recently, we and others have reported an increased expression of additional T cell subsets, including Th17 cells, and their hallmark cytokines in the peripheral blood, serum and skin of SSc individuals. Here, we will review recent data on the presence of various T helper cells in SSc, and discuss the potential role of Th17 cells in promoting inflammatory responses while keeping fibrosis in check. An understanding of the immune abnormalities characteristic of SSc and their significance, represents a critical step towards the identification of novel therapies that could modify the course of the disease.