期刊
CIRCULATION RESEARCH
卷 114, 期 11, 页码 1772-1787出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.114.301137
关键词
adventitia; aging; atherosclerosis; autoimmune response
资金
- German Research Council (DFG) [HA 1083/15-3, HA 1083/16-1, WE 2224/5-1, FOR809, TP11]
Tertiary lymphoid organs emerge in tissues in response to nonresolving inflammation. Recent research characterized artery tertiary lymphoid organs in the aorta adventitia of aged apolipoprotein E-deficient mice. The atherosclerosis-associated lymphocyte aggregates are organized into distinct compartments, including separate T-cell areas harboring conventional, monocyte-derived, lymphoid, and plasmacytoid dendritic cells, as well as activated T-cell effectors and memory cells; B-cell follicles containing follicular dendritic cells in activated germinal centers; and peripheral niches of plasma cells. Artery tertiary lymphoid organs show marked neoangiogenesis, aberrant lymphangiogenesis, and extensive induction of high endothelial venules. Moreover, newly formed lymph node-like conduits connect the external lamina with high endothelial venules in T-cell areas and also extend into germinal centers. Mouse artery tertiary lymphoid organs recruit large numbers of naive T cells and harbor lymphocyte subsets with opposing activities, including CD4(+) and CD8(+) effector and memory T cells, natural and induced CD4(+) regulatory T cells, and memory B cells at different stages of differentiation. These data suggest that artery tertiary lymphoid organs participate in primary immune responses and organize T-and B-cell autoimmune responses in advanced atherosclerosis. In this review, we discuss the novel concept that pro-and antiatherogenic immune responses toward unknown arterial wall-derived autoantigens may be organized by artery tertiary lymphoid organs and that disruption of the balance between pro-and antiatherogenic immune cell subsets may trigger clinically overt atherosclerosis.
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