title: Artery Tertiary Lymphoid Organs: Powerhouses of Atherosclerosis Immunity.
abstract: 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, andde novosynthesis 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.
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
authors: Changjun
authors: C
authors: Yin
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University , Munich , Germany.
authors: Sarajo Kumar
authors: SK
authors: Mohanta
authors: Cardiovascular Research Center (CVRC), University of Virginia , Charlottesville, VA , USA.
authors: Prasad
authors: P
authors: Srikakulapu
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
authors: Christian
authors: C
authors: Weber
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University , Munich , Germany.
authors: Andreas J R
authors: AJ
authors: Habenicht
keywords: adventitia; aging; artery tertiary lymphoid organs; atherosclerosis; autoimmune responses