title: Pathogenesis of Takayasu's arteritis: a 2011 update.
abstract: While our knowledge of the pathogenesis of Takayasu's arteritis (TA) has considerably improved during the last decade, the exact pathogenic sequence remains to be elucidated. It is now hypothesised that an unknown stimulus triggers the expression of the 65kDa Heat-shock protein in the aortic tissue which, in turn, induces the Major Histocompatibility Class I Chain-Related A (MICA) on vascular cells. The γδ T cells and NK cells expressing NKG2D receptors recognize MICA on vascular smooth muscle cells and release perforin, resulting in acute vascular inflammation. Pro-inflammatory cytokines are released and increase the recruitment of mononuclear cells within the vascular wall. T cells infiltrate and recognize one or a few antigens presented by a shared epitope, which is associated with specific major Histocompatibility Complex alleles on the dendritic cells, these latter being activated through Toll-like receptors. Th1 lymphocytes drive the formation of giant cells through the production of interferon-γ, and activate macrophages with release of VEGF resulting in increased neovascularisation and PDGF, resulting in smooth muscle migration and intimal proliferation. Th17 cells induced by the IL-23 microenvironnement also contribute to vascular lesions through activation of infiltrating neutrophils. Although still controversial, dendritic cells may cooperate with B lymphocytes and trigger the production of anti-endothelial cell auto-antibodies resulting in complement-dependent cytotoxicity against endothelial cells. In a near future, novel drugs specifically designed to target some of the pathogenic mechanisms described above could be expanding the physician's therapeutic arsenal in Takayasu's arteritis.
authors.affiliation: Department of Internal Medicine. French Reference Center for Rare Auto-immune diseases. Groupe hospitalier Pitié-Salpêtrière, AP-HP, 47-83 bd. de l'hôpital, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnaud
authors.forename: Julien
authors.initials: J
authors.lastname: Haroche
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.forename: Guy
authors.initials: G
authors.lastname: Gorochov
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
mesh_terms: D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006360:Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D007111:Immunity, Cellular; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D013625:Takayasu Arteritis / Q000276:immunology* / Q000503:physiopathology*
chemical_list: D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A