Epithelial cells, the cells that make the skin and envelop organs, are usually considered the shield of the body. But for Anukul Shenoy, Ph.D., an assistant professor who joined M&I and the Division of Pulmonary and Critical Care Medicine in April 2023, epithelial cells of the lungs are equally if not more essential to our survival since they help us breathe, fight against inhaled pathogens and repair damaged lungs.
Adult human lungs filter an average of 11,000 liters of air, every day. They are constantly exposed to environmental insults (pathogens, pollen, allergens, fungi, pollutants, etc.), and are the interface between the environment and our blood circulation. Among the cells that are directly exposed to this bombardment of insults are the lung epithelial cells. These cells fold and intertwine with each other to make the surface of the lungs that if unfolded would cover an area approximately the size of a tennis court! With such a large contact surface, lung epithelial cells not only function as physical barriers but also act as a direct interface between inhaled agents and our immune system that fight pathogens. Dr. Shenoy is interested in getting a better understanding of how the lung epithelial cells act as mediator of this complex communication between the external world and the lung structural and immune (innate and adaptive) cells during health and disease.
In a Nature Communication article (2021), Dr. Shenoy and his colleagues in Dr. Joseph Mizgerd’s lab at Boston University School of Medicine, discovered that lung epithelial cells can capture inhaled pathogens, and provide location -and function- related cues to our CD4 T cells via a process termed as “antigen presentation” within the lungs. In a previous article in Mucosal Immunology, (2020), Dr. Shenoy and colleagues also found that the lung epithelial cells were not only important to instruct the T cells but were also key to gather messages (IL17A molecules) from the T cells and quickly holler in the neutrophils that would rapidly eliminate the inhaled pathogens. Together, these studies demonstrate that epithelial-T cell interactions are core elements of an optimal lung barrier immunity.
“Pulmonary epithelial cells are an integral part of the immune system arsenal.” —Anukul Shenoy, Ph.D.
Dr. Shenoy is also interested in how lungs repair after an infection. It turns out that here as well, epithelial cells play an important role: many lung epithelial cells are stem cells and repair damages caused to the lung due to an infection.
Dr. Shenoy started his career as a microbiologist, studying the consequences of bacterial pneumonia in the heart, before turning to immunology. He graduated with an MS in Biotechnology from Ruia College, University of Mumbai, India, and received his doctorate from the University of Alabama at Birmingham. His doctoral work focused on understanding host-pathogen interactions during pneumococcal infections of the heart. In 2018, he joined Dr. Joseph Mizgerd’s lab as a postdoctoral scientist at the Pulmonary Center, Boston University School of Medicine where he studied the cellular and molecular mechanisms underlying lung epithelial and resident CD4 T cell communication.
At the University of Michigan, Dr. Shenoy will continue his work on the immune instructive and/or tissue reparative functions of lung epithelial cells. He will also search for potential epithelial targets that can be modulated to render the lung as a more hospitable and resilient niche for mucosal vaccine induced immune cells. That way the immune cells would already be located in the susceptible areas for pathogens, and would be faster to fight these and minimize damage than with a systemic vaccine.
Dr. Shenoy is thrilled to be joining M&I and the Division of Pulmonary and Critical Care Medicine where he already knows several colleagues. He looks forward to the many collaborations that will further contribute to our understanding of epithelial functions in maintenance of barrier immunity and health.
Outside the lab, Dr. Shenoy is looking forward to swimming at the U-M natatorium facility and playing soccer around Ann Arbor.
Shenoy, A.T., Lyon De Ana, C., Arafa, E.I. et al. Antigen presentation by lung epithelial cells directs CD4+ TRM cell function and regulates barrier immunity. Nat Commun 12, 5834 (2021). https://doi.org/10.1038/s41467-021-26045-w
Shenoy, A.T.*, Wasserman, G.A.*, Arafa, E.I., et al. Lung CD4+ resident memory T cells remodel epithelial responses to accelerate neutrophil recruitment during pneumonia. Mucosal Immunol. (2020) Mar;13(2):334-343. https://doi.org/10.1038/s41385-019-0229-2