T-Cells and B-Cells in Systemic Sclerosis

Lazaros      I. Sakkas; Chris      D. Platsoucas

doi:10.2174/157339710793205657

Abstract

Systemic sclerosis (SSc) is characterized by activation of fibroblasts with extensive deposition of collagen, by small vessel vasculopathy with fibrointimal proliferation, and activation of the immune system, with hyper-γ- globulinaemia and autoantibodies. Twin studies have shown that genetic factors play a minor role in SSc development. Serum autoantibodies and skin lymphocytic infiltrates and small vessel damage occur very early before the appearance of skin fibrosis. T cells can cause fibrosis and vasculopathy through cell-cell contact and cytokines. They produce TH2 cytokines (IL-4, IL13) and TH17 cytokines (IL-17), which are profibrotic. TH2 cells in experimental models also induce pulmonary arterial hypertension. Genetically engineered TGFβ expression in pig arteries causes fibrointimal proliferation. T cells in skin lesions exhibit oligoclonality that persists over time, which indicates an antigen-driven T cell activation, but the antigen(s) responsible are not known. There are known environmental factors that can elicit an immune response and cause a SSc-like disease. T cells also provide help for B cells. B cells can contribute to fibrosis and vasculopathy through cytokines and autoantibodies. Autoantibodies can activate endothelial cells and fibroblasts to a profibrotic phenotype. Finally, treatments directed against T cells and B cells show promising effects in SSc.

Keywords: Systemic sclerosis, T-cells, B-cells, autoantibodies, small vessel vasculopathy, fibrointimal proliferation, hyper-γ-globulinaemia, cytokines (IL-4, IL13), TH17 cytokines (IL-17), engineered TGFβ expression, SSc-like disease, chronic autoimmune disease, Raynaud's phenomenon, pulmonary arterial hyper-tension (PAH), monozygotic twins, TH17 type (IL-17), IL-6 plus OX40/OX40L axis inhibit T-regulatory cells, antigen-driven proliferation, anti-fibroblast antibo-dies, anti-endothelial cell antibodies, anti-platelet-derived growth factor (PDGF), anti-DNA topoisomerase I, anti-centromere antibodies, anti-fibrillin-1 antibodies, anti-topo-I Abs, murine topoisomerase, Anti-CMV antibodies, fibrogenic phenotype, TGFβ-dependent, CCL2 (MCP-1), Anti-topo I autoantibodies, ICAM-1, Anti-PDGF, Anti-endothelial cell, VASCULOPATHY, Aspergillus fumigatus antigen, Anti-angiotensin II type-1, Allograft inflammatory factor-1 (AIF-1), tight-skin mouse, Tight-skin (TSK) mouse, Lymphocyte infiltrates, anti-CD20, Bleomycin-Induced, CD40L, (TLR)-4, LPS, Chronic Graft-versus-Host Induced, anti-PDGFR, GVHD, B10.D2, BALB/c, anti-Scl-70, (UCD) Chickens, vascular occlusion, perivascular lymphocytic, haematopoietic stem cell transplantation (HSCT), signal transduction, bleomycin-induced fibrosis, Anti-TNFα