CD73+ Epithelial Progenitor Cells That Contribute to Homeostasis and Renewal Are Depleted in Eosinophilic Esophagitis
Takeo Hara, Yuta Kasagi, Joshua Wang, Masaru Sasaki, Bailey Aaron, Adam Karami, Masataka Shimonosono, Rieko Shimonosono, Hisatsugu Maekawa, Lauren Dolinsky, Benjamin J. Wilkins, Jeremy Klein, Jane Wei, Kathryn L. Nunes, Kristle L. Lynch, Jonathan M. Spergel, Kathryn E. Hamilton, Melanie A. Ruffner, Tatiana A. Karakasheva, Kelly A. Whelan, Hiroshi Nakagawa, Amanda B. Muir
Abstract
BACKGROUND & AIMS: cells within the basal population of human esophageal epithelium and clarified the biological significance of these cells in the EoE epithelium. METHODS: populations and seeded these groups in organoid culture to evaluate the organoid formation rate and organoid size. We used RNA interference to knock down CD73 in esophageal organoids to evaluate organoid formation rates and size. We evaluated the effects of signal transducer and activator of transcription 6 (STAT6) signaling inhibition by RNA interference, a STAT6 inhibitor, AS1517499, as well as the proton pump inhibitor omeprazole. RESULTS: population. CONCLUSIONS: self-renewal population by helper T cell 2 cytokines in EoE milieu may be perpetuating epithelial injury. Future therapies targeting epithelial restitution in EoE could decrease the need for immune modulation and steroid therapy.