Knowns and unknowns of tissue-resident memory T cells

Advances in transcriptomics and other approaches are shedding considerable light on tissue-resident immune cells as distinct from recirculating cells. The advances encompass antigen-presenting cell subsets, Tregs and importantly, tissue-resident memory cells (TRM). What are the transcriptional programmes and functional properties that distinguish the requirements for an effective tissue resident cell in brain relative to lung, skin, adipose tissue or the genital tract? Another important conundrum has been the extent to which TRM cells are specialized either as a sense and alarm' population or as a local, primed, effector cell population in themselves. These are questions that challenge immunologists to stop thinking in terms of a generic, model, immune response and focus instead on events in the tissue in question.