Single-Cell RNA Seq Reveals Cells Driving EoE While Raising Questions about Butyrate

Published April 8, 2019 | Journal of Clinical Investigation

An eight-year hunt for the cells that drive the extreme childhood food allergy eosinophilic esophagitis (EoE) has identified a potential new way to treat the disease while also raising questions about a dietary supplement often taken to reduce bowel inflammation.

The study was led by first author Ting Wen, MD, PhD, and senior author Marc Rothenberg, MD, PhD, director of the Division of Allergy and Immunology, a renowned authority whose work helped establish EoE as its own disorder.

In this study, Wen and Rothenberg developed and perfected a same-day process to isolate individual living cells from human esophageal tissue samples and analyze them quickly using single-cell RNA sequencing technology.

“This is a substantial advance for the field,” Rothenberg says. “Prior work has focused on blood cells, but not the specific memory immune cells in tissue that directly respond to food allergens.”

They report finding eight types of immune system T cells in esophageal tissue. Two cell types (T7 and T8) were elevated in diseased tissue. T8 cells were nearly non-existent in healthy tissue, suggesting they may be a target for treatment.

In a surprising result, the study reports that the gene FFAR3 is over-expressed in diseased tissue and appears to help trigger the inflammation response. This same gene also encodes a receptor for the dietary supplement butyrate.

Many people with inflammatory bowel conditions find benefit from butyrate, but the supplement appears to have a different effect in the esophagus. “It is far too early to say under which or any conditions butyrate could be harmful,” Rothenberg says. “But this initial discovery deserves further exploration.”