title: The role of the acquired immune response in systemic sclerosis.
abstract: Profound alterations characterize the adaptive immune response in systemic sclerosis, and several layers of evidence support a prominent role exerted by immune cellular effectors and humoral mediators in the pathogenesis of this disease. These include (i) the presence of oligoclonal T cells in tissues undergoing fibrosis consistent with (auto)antigen-specific recruitment, (ii) the preferential expansion of polarized CD4+ and CD8+ T cells producing pro-fibrotic cytokines such as IL-4 and IL-13, (iii) the presence of increased number of cells producing mediators belonging to the IL-17 family, including IL-22, which may drive and participate in inflammatory pathways involving epithelial cells as well as fibroblasts, (iv) the deficient or redirected function of T regulatory cells favoring fibrosis, and (v) the enhanced expression of CD19 and CD21 on naïve B cells, and the upregulation of co-stimulatory molecules in mature B cells, which together with the increased levels of B cell activating factor (BAFF) underlie the propensity to an exaggerated humoral response possibly favoring fibrogenesis. Despite all the progress made in understanding the features of the aberrant immune response in scleroderma, it remains unclear whether the activation of immune effector pathways ultimately drives the disease pathogenesis or rather represents a defective attempt to limit or even reverse excessive extracellular matrix deposition and progressive vasculopathy, the main hallmarks of this disease.
authors.affiliation: Immunology and Allergy, University Hospital and School of Medicine, Rue Gabrielle Perret-Gentil 4, 1211, Geneva 14, Switzerland, Carlo.Chizzolini@unige.ch.
authors.forename: Carlo
authors.initials: C
authors.lastname: Chizzolini
authors.forename: Francesco
authors.initials: F
authors.lastname: Boin
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines