PTPN2 Loss in Intestinal Epithelial Cells Increases ACE2 Expression in the Lung

SARS-CoV-2, a betacoronavirus notable for its cause of the COVID-19 pandemic, is a prevalent viral pathogen that has affected millions of individuals worldwide. Particular individuals have a predisposed high risk for a severe COVID-19 infection, including those affected by Inflammatory Bowel Disease (IBD), an autoimmune disease characterized by chronic gut inflammation. PTPN2, a major regulator of the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway, is a leading cause of IBD, creating a highly inflammatory environment when exhibiting loss-of-function. Previous research in our lab has shown cells lacking PTPN2 in vitro increase ACE2 expression and viral-like particle (VLP) uptake in intestinal epithelial and lung cell lines. In vivo measurements of Ace2 in Ptpn2-/- mice showed elevation in the intestinal epithelial cells (IEC), heart, and lung, both in transcriptional and translational expression. These findings propose a link between COVID-19 and IBD as ACE2 acts as an entry receptor for the virus into the host cell. Our recent findings further this link, as the intestinal Ptpn2ΔIEC mice model shows increased Ace2 expression in lung whole tissue (p=0.0241, n=3), and a trend of increased viral uptake when infected with the SARS-CoV-2 MA10 strain (p=0.0874, n=3). Our intranasally infected Ptpn2ΔIEC mouse model also relates to the common reports of COVID-19 intestinal symptoms, as we observe an increase in luminal fluid from infected wild type mice in the cecum, which ties to increased diarrhea promotion when IBD is combined with COVID-19 (p=0.0087, n=3). In conclusion, our data indicates that intestinal epithelial PTPN2 impacts expression of an important viral receptor in the lung, thus revealing a novel contribution to the gut-lung axis. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.