This research focuses on understanding how certain immune responses can lead to chronic lung conditions after viral pneumonia, like COVID-19. We and others identified a novel immune cell population, the CD4+ tissue-resident T cells, which stays in the lungs and helps fight off secondary viral infections. However, the role of these cells in maintaining lung health and in disease conditions is not fully understood. The study also found that a particular cytokine, IL-21, produced by these cells, plays a role in managing the lung’s immune cell network. The research aims to explore if modulating this cell population and its by-products can control chronic lung sequelae post viral pneumonia. The successful completion of this study could significantly enhance our understanding of the cellular and molecular basis of chronic lung diseases post vial pneumonia and could lead to new ways to prevent or treat these conditions, especially in patients with Post-Acute Sequelae of SARS-CoV-2 infection.
Respiratory viral infections such as influenza and SARS-CoV-2 can lead to the development of chronic lung disease and long-termly impaired lung function after recovery from acute morbidity. For instance, a huge number of patients are suffering from the post- acute sequelae of SARS-CoV-2 (PASC} or long COVID in the recent COVID-19 pandemic. However, the mechanisms underlying the development of chronic diseases post-acute respiratory viral infection are largely elusive.
Previously, we found that the excessive accumulation of CD8+ tissue-resident T cells (TRM} caused long-term tissue inflammation and fibrosis, leading to diminished lung function in a model of chronic lung sequelae post-acute viral pneumonia during aging. In addition, we recently identified that the population of lung resident CD4+ T helper cells (TRH}, which can provide local help for CD8+ TRM maintenance, were greatly increased following viral pneumonia. Furthermore, TRH cell presence was associated with the development of chronic lung sequelae in COVID-19 convalescents. Based on these exciting prelim data, we hypothesize that dysregulated TRH responses promote excessive CD8+ TRM accumulation, thereby leading to the development of chronic lung conditions following acute viral pneumonia. Furthermore, we will test the therapeutic potential of targeting IL-21 produced by TRH cells in dampening chronic tissue sequelae post-acute viral morbidity. We believe that the successful completion of this study will not only advance our current understanding on the cellular and molecular mechanisms underlying chronic lung sequelae occurrence following viral pneumonia, but also pave the way to develop novel preventive and/or therapeutic options treating chronic lung diseases following acute viral pneumonia.