Trapping of misdirected dendritic cells in the granulomatous lesions of giant cell arteritis.
Immature dendritic cells (DCs) are scattered throughout peripheral tissues and act as sentinels that sample the antigenic environment. After activation, they modify their chemokine receptor profile and migrate toward lymphoid tissues. On arrival, they have matured into chemokine-producing DCs that express co-stimulatory molecules and can prime naive T cells. Normal temporal arteries contain immature DCs that are located at the media-adventitia border. In temporal arteries affected by giant cell arteritis, DCs are highly enriched and activated and have matured into fully differentiated cells producing the chemokines, CCL18, CCL19, and CCL21. In keeping with their advanced maturation, DCs in the granulomatous lesions possess the chemokine receptor, CCR7. CCR7 binds CCL19 and CCL21, causing the highly activated DCs to be trapped in the peripheral tissue site. The co-stimulatory molecule, CD86, which is critical for DC/T-cell interaction, is expressed by a subset of DCs captured in the arterial wall. DC/T-cell interaction does not involve interleukin-12; transcripts for interleukin-12 p40 are absent in the vasculitic infiltrates. We propose that differentiation of DCs and the autocrine and paracrine actions of chemokines in granulomatous lesions misdirect DCs away from their usual journey to lymphoid organs and are critical in maintaining T-cell activation and granuloma formation in giant cell arteritis.
Krupa
Wei Ma
WM
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Dewan
Misha
M
Jeon
Myung-Shin
MS
Kurtin
Paul J
PJ
Younge
Brian R
BR
Goronzy
Jörg J
JJ
Weyand
Cornelia M
CM
D000368:Aged; D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D001167:Arteritis / Q000276:immunology* / Q000473:pathology; D051940:B7-2 Antigen; D002465:Cell Movement; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology*; D005260:Female; D006101:Granuloma, Giant Cell / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology; D010641:Phenotype; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis
D015703:Antigens, CD; D051940:B7-2 Antigen; C515370:CCR7 protein, human; C497964:CD86 protein, human; D018925:Chemokines; D008562:Membrane Glycoproteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine