Inflammation and immunity

Abstract

Systemic sclerosis (SSc) is considered an autoimmune systemic disorder as reflected by the high prevalence of autoantibodies in the sera of individuals suffering from SSc. In addition, several clinical features, gene polymorphisms, and biological abnormalities characteristically present in SSc are also shared with other autoimmune systemic conditions such as systemic lupus erythematosus (SLE). They include gene polymorphisms associated with the immune response and the production of type I interferon upon activation of Toll-like receptors. It should be noted though that there is no established animal model able to reproduce the clinical phenotype of SSc upon immunization or passive transfer of immune cells or antibodies. During the last several decades, an enormous body of work has been generated indicating that different cells and soluble mediators belonging to the innate and adaptive immune system present abnormalities which are associated with distinct SSc phenotypes and that are possibly linked to disease development and progression. Strong evidence implicates dysregulated IL-1 family members and IL-6 function, skewed T cell responses toward a Th2 functional phenotype, and the preferential production of chemokines with pro-fibrotic potential. T cells have been shown to recognize autoantigens, some of which may result from cross-reactivity with neo-epitopes generated during cancer development. Despite this solid experimental evidence, it remains challenging to decipher with precision the sequence of events leading to a perturbed immunological state in scleroderma and attribute them a causal rather than a consequential role.