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

Tissue-resident memory T (T_RM) cells are increasingly associated with the outcomes of health and disease. T_RM cells can mediate local immune protection against infections and cancer, which has led to interest in T_RM 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 T_RM cells established in animal models and in translational human studies. We review the beneficial effects of T_RM cells in mediating protective responses against infection and cancer and the adverse role of T_RM cells in driving pathology in autoimmunity. A further understanding of the breadth and mechanisms of T_RM cell activity is essential for the safe design of strategies that manipulate T_RM cells, such that protective responses can be enhanced without unwanted tissue damage, and pathogenic T_RM cells can be eliminated without losing local immunity.