Propionate Alleviates Abdominal Aortic Aneurysm by Modulating Colonic Regulatory T-Cell Expansion and Recirculation

• SCFAs alleviate the progression of AAA in both Ca 3 (PO 4 ) 2 - and elastase-induced mouse AAA models. • Propionate expands the pool of Tregs in the cLP and enhances the cell-intrinsic ability of cLP-Tregs to recirculate by downregulating CD69 expression on the surface of cLP-Tregs. • Propionate facilitates the recirculation of cLP-Tregs from the cLP through colonic dLNs and circulating blood to the inflamed aneurysm to mitigate AAA. Emerging evidence supports that intestinal microbial metabolite short-chain fatty acids (SCFAs) increase the pool of regulatory T cells (Tregs) in the colonic lamina propria (cLP) and protect against nonintestinal inflammatory diseases, such as atherosclerosis and post-infarction myocardial inflammation. However, whether and how SCFAs protect the inflamed aortas of subjects with abdominal aortic aneurysm (AAA) remains unclear. Here, the authors revealed the protective effect of SCFAs on AAA in mice and the expansion of Tregs in the cLP, and propionate exerted Treg-dependent protection against AAA by promoting the recirculation of cLP-Tregs through colonic draining lymph nodes (dLNs) to the inflamed aorta.