Tuft Cell Expression Changes with Sleeping, Eating Cycles

A team of researchers from Carnegie Mellon University's Department of Biological Sciences and the University of Texas Southwestern Medical Center have uncovered how a subset of cells in the intestines change throughout the day.

"We found abundance of the sentinel tuft cells is higher at dusk, the beginning of the active phase, and low at dawn, the beginning of the resting phase," said Jianglin Zhang, a postdoctoral fellow in biological sciences at Carnegie Mellon and first author on a paper published in Science Immunology. "However, if feeding times were reversed, the abundance of tuft cells was also reversed."

Tuft cells are found in the lining of the intestines and are implicated in monitoring the immune systems. They survey the gut's luminal environment and signal other cells if they detect potential immune threats.

To study these cells, the researchers studied mice infected with parasites and viruses on various feeding schedules. They then measured changes in tuft cells and various signals.

"We were the first to study tuft cell biology across day-night cycles," said Zheng Kuang, assistant professor of biological sciences at Carnegie Mellon. "It was extremely labor intensive and required extra caution to study this process in both the daytime and nighttime."

The researchers found that HDAC3, a histone modifying enzyme, promotes the creation of tuft cells and the changes in abundance throughout the day. They also found changes to a developmental pathway that HDAC3 targets reduces the amount of tuft cells and reduces the body's ability to fight infections.

"Tuft cells play key roles in immunity and are also implicated in diseases including obesity, inflammatory bowel disease and colorectal cancer," Kuang said. "Our findings suggest new avenues for fighting against these diseases by targeting these tuft cells."

The researchers plan to further study the implications of tuft cell rhythms in healthy and diseased mice.

Zhang and Kuang were joined by Junjie Ma, Yiran Duan, Samskrathi Sharma, Sarah Oladejo, Xianda Ma and Giselle Arellano from Carnegie Mellon and Guoxun Wang, Robert Orchard and Tiffany Reese from the University of Texas on "HDAC3 Integrates TGF-β and Microbial Cues to Program Tuft Cell Biogenesis and Diurnal Rhythms in Mucosal Immune Surveillance." Their work was funded by the National Institutes of Health, the Charles E. Kaufman Foundation and the Shurl and Kay Curci Foundation.