Doublecortin‐like kinase 1‐positive enterocyte – a new cell type in human intestine

Abstract

Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated kinase. In murine intestine, DCLK1 marks tuft cells with characteristic microvilli, features of neuroendocrine cells and also quiescent stem cell-like properties. The occurrence and pathological role of DCLK1-positive cells in human intestinal mucosa is unknown. We analysed DCLK1 expression in healthy duodenal, jejunal and colorectal mucosa samples (n = 35), and in duodenal specimens from patients with coeliac disease (n = 20). The samples were immunohistochemically double-stained with DCLK1, and synaptophysin, chromogranin A and Ki-67. Ultrastructure of DCLK1-expressing duodenal cells was assessed using correlative light and electron microscopy. DCLK1 expression was seen in about 1% of epithelial cells diffusely scattered through the intestinal epithelium. Electron microscopy showed that the duodenal DCLK1-positive cells had short apical microvilli similar to neighbouring enterocytes and cytoplasmic granules on the basal side. DCLK1-positive cells were stained with synaptophysin. The number of DCLK1-positive cells was decreased in villus atrophy in coeliac disease. Our findings indicate that in human intestinal epithelium, DLCK1-positive cells form a subpopulation of non-proliferating neuroendocrine cells with apical brush border similar to that in enterocytes, and their number is decreased in untreated coeliac disease.

Distribution pattern and molecular signature of cholinergic tuft cells in human gastro-intestinal and pancreatic-biliary tract

“…The serine/threonine-protein kinase, doublecortin-like kinase 1 (Dclk1), is an established tuft cell marker in the mouse alimentary tract 7,44 , but recently was described to be restricted to a subset of enteroendocrine cells in the human intestine 45 . Using the same antiserum, we could confirm that DCLK1 is expressed by ChAT-ir tuft cells in the mouse gastro-intestinal system (data not shown).…”

Gene Expression of Transient Receptor Potential Channels in Peripheral Blood Mononuclear Cells of Inflammatory Bowel Disease Patients

“…This finding suggests that TRPM5 plays an important role in regulating the intestinal inflammatory response and epithelial integrity. Another study showed that the number of DCLK1-positive cells decreased in intestinal tissue from patients with celiac disease [ 45 ]. Meanwhile, our study found no alteration in TRPM5 expression in PBMCs from either UC or CD patients, warranting further investigation.…”

Tuft Cells: A New Player in Hirschsprung's Disease

“…They did not show morphological features typical to tuft cells, as reported in animal studies, 1,2 but instead showed an apical brush border of even thickness. 3 In the duodenum, they found colocalization of synaptophysin and DCLK1, suggesting a neuroendocrine role for these cells in this region.…”

“…1,2 A recent paper by Leppänen et al documented the expression of DCLK1-positive enterocytes in the human intestine for the first time. 3 Tuft cells were found along the entire length of the human gastrointestinal (GI) tract. These cells were seen to be scattered between the crypts and villi, with DCLK1 expressed on the basal pole of each cell.…”