Pathogenesis of giant cell arteritis: More than just an inflammatory condition?
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.
Ly
Kim-Heang
KH
Université Paris Descartes, Institut Cochin, INSERM U, Paris, France.
Régent
Alexis
A
Tamby
Mathieu C
MC
Mouthon
Luc
L
D000818:Animals; D001158:Arteries / Q000473:pathology*; D015551:Autoimmunity; D002450:Cell Communication; D004730:Endothelium, Vascular / Q000473:pathology; D013700:Giant Cell Arteritis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation; D008264:Macrophages / Q000276:immunology; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology