Numerous innate and adaptive immune cells reside in non-lymphoid tissues, where they contribute to barrier immunity, tissue homeostasis, and immune regulation. These tissue-resident populations do not recirculate in the blood or lymphatics and adopt a unique phenotype that is distinct from immune cells in the circulation. Tissue residency has been predominantly described for memory CD8+ T cells [tissue-resident memory T cells (TRM)], but it is now clear that CD4 T cells, regulatory T (Treg) cells, various innate T cells, and innate lymphoid cells (ILCs) can establish residence in non-lymphoid tissues. Here we highlight distinct and common features of tissue-resident lymphocytes, with a focus on the transcriptional programs that have recently been shown to guide the establishment of tissue residency.
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