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

APMIS. 2016 Nov;124(11):958-965. doi: 10.1111/apm.12599. Epub 2016 Sep 28.

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.

Keywords: Doublecortin-like kinase 1; duodenum; electron microscope; immunohistochemistry; synaptophysin.

MeSH terms

  • Adult
  • Aged
  • Celiac Disease / pathology
  • Chromogranin A / analysis
  • Cytoplasmic Granules / ultrastructure
  • Doublecortin-Like Kinases
  • Duodenum / cytology*
  • Enterocytes / chemistry*
  • Enterocytes / classification*
  • Enterocytes / ultrastructure
  • Female
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / cytology*
  • Intestine, Large / cytology*
  • Intracellular Signaling Peptides and Proteins / analysis*
  • Jejunum / cytology*
  • Ki-67 Antigen / analysis
  • Male
  • Microscopy
  • Microvilli / ultrastructure
  • Middle Aged
  • Protein Serine-Threonine Kinases / analysis*
  • Synaptophysin / analysis
  • Young Adult

Substances

  • CHGA protein, human
  • Chromogranin A
  • Intracellular Signaling Peptides and Proteins
  • Ki-67 Antigen
  • SYP protein, human
  • Synaptophysin
  • DCLK1 protein, human
  • Doublecortin-Like Kinases
  • Protein Serine-Threonine Kinases