The Multifaceted Role of Tissue-Resident Memory T Cells

Regionalized immune surveillance relies on the concerted efforts of diverse memory T cell populations. Of these, tissue-resident memory T (T_RM) cells are strategically positioned in barrier tissues, where they enable efficient frontline defense against infections and cancer. However, the long-term persistence of these cells has been implicated in a variety of immune-mediated pathologies. Consequently, modulating T_RM cell populations represents an attractive strategy for novel vaccination and therapeutic interventions against tissue-based diseases. Here, we provide an updated overview of T_RM cell heterogeneity and function across tissues and disease states. We discuss mechanisms of T_RM cell-mediated immune protection and their potential contributions to autoimmune disorders. Finally, we examine how T_RM cell responses might be durably boosted or dampened for therapeutic gain.