Artery tertiary lymphoid organs in atherosclerosis: A review

Atherosclerosis (AS) is the common pathological basis for many cardiovascular diseases. Initial investigations into AS predominantly centered on endothelial immune responses associated with plaque formation. However, recent studies increasingly underscore the salutary immune modulation occurring on the aorta adventitia as the atheromatous plaque progresses. The immune responses extend from the intima of the vessel to the adventitia, and the artery tertiary lymphoid organ (ATLO) assumes a major immune role in advanced stages of AS, according to available studies conducted on ApoE^-/- mice. In this review, we collate the history of studies on the participation of ATLOs in immunity to AS, detailing its structure, classification, cellular composition, and formation mechanisms. We elucidate the distinct roles of ATLO components in immune regulation, emphasizing unique features such as territorial organization, T cell-driven autoimmunity, and the T follicular helper-germinal center B cell axis, which distinguish ATLOs from conventional lymphoid responses. Furthermore, based on the latest research, we propose that ATLOs cooperate with the nervous system to regulate the progression of AS. Moreover, we highlight that aging has a great impact on the deterioration of AS and this impact is related to ATLOs. We conclude by suggesting that a focus on ATLOs is important for the clinical management of AS, and we offer a perspective for further research on ATLO and suggest whether it will be beneficial or detrimental to ATLOs.