Tissue-resident memory T cells and lung immunopathology

Rapid reaction to microbes invading mucosal tissues is key to protect the host against disease. Respiratory tissue-resident memory T (T-RM) cells provide superior immunity against pathogen infection and/or re-infection, due to their presence at the site of pathogen entry. However, there has been emerging evidence that exuberant T-RM-cell responses contribute to the development of various chronic respiratory conditions including pulmonary sequelae post-acute viral infections. In this review, we have described the characteristics of respiratory T-RM cells and processes underlying their development and maintenance. We have reviewed T-RM-cell protective functions against various respiratory pathogens as well as their pathological activities in chronic lung conditions including post-viral pulmonary sequelae. Furthermore, we have discussed potential mechanisms regulating the pathological activity of T-RM cells and proposed therapeutic strategies to alleviate T-RM-cell-mediated lung immunopathology. We hope that this review provides insights toward the development of future vaccines or interventions that can harness the superior protective abilities of T-RM cells, while minimizing the potential for immunopathology, a particularly important topic in the era of coronavirus disease 2019 (COVID-19) pandemic.