Abstract
Despite considerable recent insight into the molecular phenotypes and type 2 innate immune functions of tuft cells in rodents, there is sparse knowledge about the region-specific presence and molecular phenotypes of tuft cells in the human digestive tract. Here, we traced cholinergic tuft cells throughout the human alimentary tract with immunohistochemistry and deciphered their region-specific distribution and biomolecule coexistence patterns. While absent from the human stomach, cholinergic tuft cells localized to villi and crypts in the small and large intestines. In the biliary tract, they were present in the epithelium of extra-hepatic peribiliary glands, but not observed in the epithelia of the gall bladder and the common duct of the biliary tract. In the pancreas, solitary cholinergic tuft cells were frequently observed in the epithelia of small and medium-size intra- and inter-lobular ducts, while they were absent from acinar cells and from the main pancreatic duct. Double immunofluorescence revealed co-expression of choline acetyltransferase with structural (cytokeratin 18, villin, advillin) tuft cell markers and eicosanoid signaling (cyclooxygenase 1, hematopoietic prostaglandin D synthase, 5-lipoxygenase activating protein) biomolecules. Our results indicate that region-specific cholinergic signaling of tuft cells plays a role in mucosal immunity in health and disease, especially in infection and cancer.
Highlights
Despite considerable recent insight into the molecular phenotypes and type 2 innate immune functions of tuft cells in rodents, there is sparse knowledge about the region-specific presence and molecular phenotypes of tuft cells in the human digestive tract
The present study provides the first characterization of the cholinergic tuft cell system in the human gastro-entero-pancreatic and extrahepatic biliary tract
Immunohistochemistry for the cholinergic marker enzyme, choline www.nature.com/scientificreports acetyltransferase (ChAT), revealed that ChAT serves as a reliable tuft cell marker throughout the human entero-pancreatic and extrahepatic biliary systems, and highlights the central role ACh may play in the diverse functions that recently have been assigned to tuft cells
Summary
Despite considerable recent insight into the molecular phenotypes and type 2 innate immune functions of tuft cells in rodents, there is sparse knowledge about the region-specific presence and molecular phenotypes of tuft cells in the human digestive tract. Transgenic mice that produce enhanced green fluorescent protein (EGFP) under the control of the ChAT promoter[27,28] are useful tools to visualize cholinergic tuft cells It is still under debate, if classical taste and gastro-intestinal tuft cells accumulate and store ACh in secretory vesicles, and require the vesicular acetylcholine transporter (VAChT), as do cholinergic neurons[29]. A presence of cells with tuft cell-like morphologies has been reported for the human gastro-intestinal tract[30,31,32], and evidence for the presence of ACh and enzymatic activity of ChAT in gut surface epithelia has been provided[33,34]. The presence of a tuft cell population in the normal human pancreatic duct system has been reported[40], a possible cholinergic co-phenotype is unknown
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