tissueresident

Tissueresident is a term used to describe cells that reside within a tissue rather than circulating through the bloodstream. In immunology, this concept encompasses a range of cell types that persist in a particular organ or barrier site for extended periods. The best-described examples are tissue-resident memory T cells (TRMs) and tissue-resident macrophages. These cells are distinct from circulating immune cells, which continually traffic through blood and lymph.

Tissue-resident macrophages originate from embryonic precursors or long-lived monocytes and maintain populations locally through self-renewal. They populate the liver (Kupffer cells), brain (microglia), skin (Langerhans cells), and lungs (alveolar macrophages). TRMs reside in skin, mucosa, and other barriers, providing rapid responses to pathogens. They express retention markers such as CD69 and often CD103, helping them stay in tissue.

Residency is maintained by local signals like IL-15 and TGF-β, transcriptional programs, and receptor downregulation of S1P1 by CD69. Turnover varies: some residents renew in situ, others persist for years with minimal replenishment. The tissue microenvironment imparts specialized phenotypes and functions.

Tissue-resident cells support immediate defense, maintain tissue integrity, and shape local immunity. They influence vaccine efficacy and are involved in chronic inflammation, fibrosis, and tumor microenvironments. Understanding tissue residency informs therapies in infection, autoimmunity, and cancer.