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 (TRM ) 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 TRM -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 TRM cells and processes underlying their development and maintenance. We have reviewed TRM -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 TRM cells and proposed therapeutic strategies to alleviate TRM -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 TRM cells, while minimizing the potential for immunopathology, a particularly important topic in the era of coronavirus disease 2019 (COVID-19) pandemic.