Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Giant cell arteritis (GCA) is a granulomatous vasculitis that selectively targets medium-sized and large arteries, especially the cranial branches of the aorta. The inflammatory activity of vascular lesions is driven by adaptive immune responses, with CD4 T cells undergoing clonal expansion in the vessel wall and releasing interferon gamma. Recent studies have described a distinctive population of dendritic cells (DCs) localized at the adventitia-media border of normal medium-sized arteries that appear to play a critical role in the initiation of vasculitis. Immune effector functions of this DC population are being examined in human artery-severe combined immunodeficient (SCID) mouse chimeras. In their constitutive form, CD11c+ fascin+ adventitial DCs are not recognized by alloreactive T cells. Triggering with Toll-like receptor (TLR) ligands is sufficient to break this state of tolerance and initiate DC activation, T-cell recruitment, T-cell activation, and T-cell retention in the arterial wall. Systemic administration of ligands for TLR2 or -4 in human artery-SCID chimeras drives differentiation of adventitial DCs into chemokine-producing effector cells with high-level expression of both CD83 and CD86 and mediates T-cell regulatory function through release of interleukin 18. In established vasculitis, fully matured DCs retain antigen-presenting function; antibody-mediated DC depletion disrupts T-cell and macrophage activation and has marked anti-inflammatory effects. We conclude that adventitial DCs, an indigenous cell population of the arterial wall, are responsive to pathogen-derived macromolecules and have gatekeeper function in regulating T-cell recruitment and retention to the arterial adventitia. A switch of adventitial DCs from being nonstimulatory to T-cell activating emerges as a critical event in the initiation of vasculitis.
 ...
PMID:Vascular dendritic cells in giant cell arteritis. 1646 2

Giant cell arteritis (GCA) is characterized by intimal hyperplasia and luminal obstruction leading to ischemic manifestations involving extra-cranial branches of carotid arteries and aorta. Histopathological lesions involve all layers of the arterial wall and are associated with multinucleated giant cells, fragmented internal elastic lamina and polymorphic cellular infiltrates, including T lymphocytes and macrophages. The pathophysiology of GCA is still poorly understood. After dendritic cell activation, CD4(+) T lymphocytes, T helper 1 (Th1) cells, produce interferon gamma and modulate macrophage activation and functions, and Th17 cells produce interleukin 17 (IL-17), which can induce cytokine production by macrophages and fibroblasts. Macrophages in the adventitia produce pro-inflammatory cytokines such as IL-1, IL-6 and tumor necrosis factor alpha. These cytokines promote arterial wall and systemic inflammation. Questions remain regarding the nature of the antigen(s) triggering dendritic cell activation and the mechanisms underlying vascular remodeling. Here we review recent advances in the pathogenesis of GCA, with emphasis on the interactions between cells of the immune system and components of the vessel wall, including vascular smooth muscle cells and endothelial cells, leading to vascular remodeling. Finally, we propose new areas of investigation that could help understand the triggering factors and key pathogenic events in GCA.
 ...
PMID:Pathogenesis of giant cell arteritis: More than just an inflammatory condition? 2045 78