A novel esophageal tolerogenic dendritic cell subset

BackgroundGastroenteric tract requires robust tolerogenic mechanisms to tolerize foreign antigens like foods and microbiota. This is critical to establish the immune homeostasis, which upon disruption, might contribute to a plethora of atopic disorders, including food allergy and eosinophilic esophagitis (EOE). Recently, there was a new subset of tolerizing dendritic cells (tolDCs), PRDM16 tolDC, discovered in the gut of mice and humans, which confers protection against food allergy. Whether an analogous population of it exist in the esophagus is unknown, especially in the context of EOE, another atopic disease associated with dietary antigens. MethodsWe thoroughly analyzed the human esophagus cell atlas single cell RNA-seq dataset and the myeloid DC-VERSE dataset, in an attempt to identify and characterize the esophageal counterpart of the intestinal PRDM16 tolDC. ResultsWe identified the esophageal counterpart of intestinal PRDM16 tolDC as a conventional type II DC subtype expressing PRDM16, termed as cDC2C (PRDM16). We demonstrated the similarities between PRDM16 tolDC and cDC2C (PRDM16) regarding their transcriptomic and functional profiles. Importantly, we found that cDC2C (PRDM16) were expanded during EOE and exhibited an anti-inflammatory phenotype, suggesting their protective role in EOE. Notably, these tolerogenic DCs were not found in other atopic diseases beyond the gastroenteric tract. ConclusionsWe here defined a novel tolerogenic DC population in human esophagus and demonstrated their implications in the pathophysiology of EOE. These findings would provide novel insights towards the tolerogenic mechanisms along the gastroenteric tract and possess translational relevance for EOE diagnosis and interventions.