A novel serotonin-containing tuft cell subpopulation in mouse intestine

In this study, a novel subset of doublecortin-like kinase 1 (DCLK1)-immunoreactive (IR) tuft cells that also contain serotonin (5-hydroxytryptamine, 5HT) is described, in terms of their number, regional distribution, possible synthesis or reuptake of 5HT and proximity to 5-HT-containing enterochromaffin (EC) cells. The small intestine from C57BL/6J mice was divided into five segments while the large intestine was kept undivided. Double immunostaining was used to estimate numbers and topographic distribution of 5HT-IR (DCLK1/5HT) tuft cells and their possible expression of tryptophan hydroxylase (TPH) and serotonin transporter (SERT). Also, possible contacts between tuft cells and 5HT-IR EC cells were studied. In the small intestine, up to 80% of all tuft cells were identified as DCLK1/5HT-IR; in the large intestine, such cells were rare. The highest number of DCLK1/5HT-IR cells was found in the upper small intestine. The numbers of DCLK1/5HT-IR cells gradually decreased distally. DCLK1-IR tuft cells were not found to contain TPH, the rate-limiting enzyme in 5HT synthesis. SERT, the selective transporter for 5HT reuptake, could not convincingly be demonstrated in tuft cells. In villi and crypts, 3% and 10%, respectively, of all DCLK1-IR cells were in close proximity to EC cells. EC cells in close proximity to DCLK1-IR cells were, in villi and crypts, 3 and 8%, respectively. We conclude that DCLK1/5HT-IR cells constitute a novel subset of tuft cells that may have unique roles in the GI tract.