Global Microbiome Congress

Abstract

The intestinal mucosal surface is directly exposed to daily fluctuations in food and microbes driven by 24-hour light and feeding cycles. Intestinal epithelial tuft cells are key sentinels that surveil the gut luminal environment, but how these cells are diurnally programmed remains unknown. Here, we show that histone deacetylase 3 (HDAC3) controls tuft cell specification and the diurnal rhythm of its biogenesis, which is regulated by the gut microbiota and feeding schedule. Disruption of epithelial HDAC3 decreases tuft cell numbers, impairing anti-helminth immunity and norovirus infection. Mechanistically, HDAC3 functions noncanonically to activate transforming growth factor–β (TGF-β) signaling, which promotes rhythmic expression of Pou2f3, a lineagedefining transcription factor of tuft cells. Our findings reveal an environmental-epigenetic link that controls the diurnal differentiation of tuft cells and promotes rhythmic mucosal surveillance and immune responses in anticipation of exogenous challenges.

Biography

Dr. Jianglin Zhang obtained his PhD at Zhejiang University in 2019 at Hangzhou, China, followed by postdoctoral studies at the University of Sourthern Carlifornia and the Carnegie Mellon University. He is currently an faculty in the Department of Biological Sciences at the Carnegie Mellon University. Dr. Jianglin Zhang has published 14 research papers in prestigious journals including Science Immunology His research focuses on the interplay between gut microbiota, epigenetic regulation, and circadian rhythm in the intestine, with particular emphasis on their roles in controlling pathogen infections and metabolic diseases.