Local heroes or villains: tissue-resident memory T cells in human health and disease

Tissue-resident memory T (TRM) cells are increasingly associated with the outcomes of health and disease. TRM cells can mediate local immune protection against infections and cancer, which has led to interest in TRM cells as targets for vaccination and immunotherapies. However, these cells have also been implicated in mediating detrimental pro-inflammatory responses in autoimmune skin diseases such as psoriasis, alopecia areata, and vitiligo. Here, we summarize the biology of TRM cells established in animal models and in translational human studies. We review the beneficial effects of TRM cells in mediating protective responses against infection and cancer and the adverse role of TRM cells in driving pathology in autoimmunity. A further understanding of the breadth and mechanisms of TRM cell activity is essential for the safe design of strategies that manipulate TRM cells, such that protective responses can be enhanced without unwanted tissue damage, and pathogenic TRM cells can be eliminated without losing local immunity.