Immune outposts in the adventitia: One foot in sea and one on shore

Advances in microscopy, genetically modified mice, and single-cell RNA sequencing have begun to deconvolute the composition and function of tissue immune niches. Here we discuss the evidence that the adventitia, the outermost layer of larger blood vessels, is a conserved niche and tissue immune outpost for multiple immune cells, including group 2 innate lymphoid cells (ILC2) and subsets of tissue-resident memory T cells, macrophages, and dendritic cells. We also describe the unique non-immune composition at adventitial regions, including fibroblast-like stromal cell subsets, lymphatic and blood endothelial cells, and neurons, and review how immune-stromal crosstalk impacts regional tissue immunity, organ adaptation, and disease.