title: Pathogenesis of giant cell arteritis: new insight into the implication of CD161+ T cells.
abstract: Giant cell arteritis (GCA) is a granulomatous large-vessel vasculitis that usually affects the aorta and/or its major branches, especially the branches of the carotid arteries. Histo-pathological lesions are observed in all layers of the artery leading to segmental and focal panarteritis with a polymorphic cell inﬁltrate that includes T cells, macrophages and multinucleated giant cells, a fragmented internal elastic lamina and intimal hyperplasia. The pathophysiology of GCA is complex and not fully understood. In this review, we discuss the immunological aspects of GCA pathogenesis with a particular emphasis on T cell responses. Upon dendritic cell activation in the adventitia, CD4 T cells co-expressing CD161 are recruited in the arterial wall and polarised into Th1 and Th17 cells that produce IFN-γ and IL-17, respectively. These cytokines activate macrophages, giant cells and vascular smooth muscle cells, thus inducing vascular remodelling which leads to the ischaemic manifestations of GCA. Macrophages inﬁltrating the adventitia produce IL-1β and IL-6, which are responsible for the general symptoms encountered in GCA.
authors.affiliation: Service de Médecine Interne et Immunologie Clinique, CHU, Dijon, France.
authors.forename: M
authors.initials: M
authors.lastname: Samson
authors.forename: S
authors.initials: S
authors.lastname: Audia
authors.forename: L
authors.initials: L
authors.lastname: Martin
authors.forename: N
authors.initials: N
authors.lastname: Janikashvili
authors.forename: B
authors.initials: B
authors.lastname: Bonnotte
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001158:Arteries / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D002634:Chemotaxis, Leukocyte; D013700:Giant Cell Arteritis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C573415:IFNG protein, human; C508600:IL6 protein, human; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D007371:Interferon-gamma