In Su Cheon, PhD

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, called 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. We also found that a particular signaling protein (cytokine), IL-21, produced by these cells, plays a role in managing the lung’s immune cell network. We will explore if altering this cell population and its by-products can control chronic lung complications after viral pneumonia. Our findings could significantly enhance our understanding of the cellular and molecular basis of chronic lung diseases after viral pneumonia and could lead to new ways to prevent or treat these conditions, especially in patients with “long COVID.”

Update: While most people recover from respiratory viruses like influenza or COVID-19, many—especially older adults—are left with scarred lungs and breathing difficulties. In our first year of Lung Association-funded research, we identified a key driver of this damage: a group of immune cells called PD-1Hi CD4+ tissue-resident helper T cells (TRH). These cells expand significantly in aged lungs after infection and release high levels of inflammatory signals like IL-21 and IL-2. By turning off a key gene in these cells, we prevented lung scarring in mice and improved lung function. Blocking IL-21 alone led to modest improvements, but our data suggest IL-2 also plays a major role. We now plan to test a dual IL-21 and IL-2 antibody treatment to better control these cells and promote full lung recovery. This work could lead to new therapies for the millions suffering from long-term lung damage after viral infections.