[HTML][HTML] Artery tertiary lymphoid organs: powerhouses of atherosclerosis immunity

C Yin, SK Mohanta, P Srikakulapu, C Weber… - Frontiers in …, 2016 - frontiersin.org
C Yin, SK Mohanta, P Srikakulapu, C Weber, AJR Habenicht
Frontiers in immunology, 2016frontiersin.org
Artery tertiary lymphoid organs (ATLOs) are atherosclerosis-associated lymphoid
aggregates with varying degrees of complexity ranging from small T/B-cell clusters to well-
structured lymph node-like though unencapsulated lymphoid tissues. ATLOs arise in the
connective tissue that surrounds diseased arteries, ie, the adventitia. ATLOs have been
identified in aged atherosclerosis-prone hyperlipidemic apolipoprotein E-deficient (ApoE−/−)
mice: they are organized into distinct immune cell compartments, including separate T-cell …
Artery tertiary lymphoid organs (ATLOs) are atherosclerosis-associated lymphoid aggregates with varying degrees of complexity ranging from small T/B-cell clusters to well-structured lymph node-like though unencapsulated lymphoid tissues. ATLOs arise in the connective tissue that surrounds diseased arteries, i.e., the adventitia. ATLOs have been identified in aged atherosclerosis-prone hyperlipidemic apolipoprotein E-deficient (ApoE−/−) mice: they are organized into distinct immune cell compartments, including separate T-cell areas, activated B-cell follicles, and plasma cell niches. Analyses of ATLO immune cell subsets indicate antigen-specific T- and B-cell immune reactions within the atherosclerotic arterial wall adventitia. Moreover, ATLOs harbor innate immune cells, including a large component of inflammatory macrophages, B-1 cells, and an aberrant set of antigen-presenting cells. There is marked neoangiogenesis, irregular lymphangiogenesis, neoformation of high endothelial venules, and de novo synthesis of lymph node-like conduits. Molecular mechanisms of ATLO formation remain to be identified though media vascular smooth muscle cells may adopt features of lymphoid tissue organizer-like cells by expressing lymphorganogenic chemokines, i.e., CXCL13 and CCL21. Although these data are consistent with the view that ATLOs participate in primary T- and B-cell responses against elusive atherosclerosis-specific autoantigens, their specific protective or disease-promoting roles remain to be identified. In this review, we discuss what is currently known about ATLOs and their potential impact on atherosclerosis and make attempts to define challenges ahead.
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