Decreased number of colonic tuft cells in quiescent ulcerative colitis patients

Abstract

Background Colonic tuft cells are epithelial chemosensory cells involved in barrier integrity, modulation of inflammatory responses and gut homeostasis. Recent evidence indicates an involvement of tuft cells in ulcerative colitis pathogenesis, though mechanisms remain largely unknown. Here, we quantified the colonic tuft cell population in patients with quiescent ulcerative colitis as compared to patients without identified colonic disease (controls). Methods In this retrospective study, we obtained endoscopic colonic sigmoid biopsies from 14 patients with quiescent ulcerative colitis and from 17 controls. In a blinded central-reading design, we identified tuft cells by immunohistochemistry using a cyclooxygenase-1 antibody as a marker and performed a simple counting by visual inspection. Poisson regression was employed for statistics and results were adjusted for gender, age and smoking status. Results Ulcerative colitis patients demonstrated a 55% reduced tuft cell count in colonic mucosa compared with the control group (95% confidence limit: range 31–71%, P = 0.0002). Ulcerative colitis patients had a mean tuft cells count of 46 tuft cells/mm 2 (95% CI, 36–59), while controls demonstrated a mean of 104 tuft cells/mm 2 (95% CI, 79–136). No interactions of other covariates, such as age, smoking status, total duration of ulcerative colitis disease and duration of clinical remission prior to study inclusion were detected between ulcerative colitis patients and controls. Conclusion Quiescent ulcerative colitis patients have a relatively low number of colonic tuft cells. Further studies are warranted to explore the potential involvement of tuft cells in ulcerative colitis pathogenesis.

Tuft Cells and Their Role in Intestinal Diseases

“…Two studies (42,43) describe a population of human colonic DCLK1 + TCs, however, Leppänen et al (44) reported that human colonic epithelial DCLK + cells have a morphology similar to absorptive enterocytes rather than a classical TC shape, thus questioning whether DCLK1 marks human TCs. In this context we recently tested a commercially available antibody (ab31704) on human colonic material, and failed to obtain convincing immunolabeling for DCLK1 (23), a conclusion also reached by Banerjee et al (40). Differences in DCLK1 immunoreactivity in human GI epithelium could be due to differences in protocol and fixation methods or that human TCs simply do not express DCLK1.…”

“…Differences in DCLK1 immunoreactivity in human GI epithelium could be due to differences in protocol and fixation methods or that human TCs simply do not express DCLK1. By contrast, cyclooxygenase enzyme (COX)-1 has been identified as a reliable marker for human TCs (9,21,23). Gerbe et al (9) were first to validate COX-1 as a marker for human TCs by co-staining for other markers such as SRY-box transcription factor 9 (SOX9) and hematopoietic prostaglandin D synthase.…”

Intestinal epithelial IPMK protects mice from experimental colitis via governing colonic tuft cell development

“…Several clinical studies have independently reported that reduced tuft cell numbers in the intestinal tract are associated with ileal Crohn's disease (Banerjee et al, 2020) and quiescent ulcerative colitis (Kjaergaard et al, 2021), suggesting that insufficient tuft cells are closely related to the pathology of inflammatory bowel diseases. Since we newly propose a IPMK-tuft cell-IBD axis in this study, targeting IPMK has the potential to be a novel therapeutic strategy to treat IBD.…”

Enteric Tuft Cells in Host-Parasite Interactions

“…While not extensive, a small number of studies have examined ETCs in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and upon enteric viral infection, prompting us to ask questions about the implications of these findings in the context of enteric parasitic infections [13,[116][117][118][119][120][121].…”

“…Thus, infection with Hymenolepis diminuta (rat cestode), Schistosoma mansoni (blood fluke/trematode parasite), and parasitic nematodes (H. polygyrus, Necator americanus (human hookworm), T. spiralis, and Trichuris suis) has been found to alleviate the severity of disease in murine models of colitis (which shares some features with human IBD) [128][129][130][131]. ETC frequency and IL-25 level were both found to be downregulated in human colonic biopsies and mouse models of colitis [13,[117][118][119], suggesting that one benefit of helminth therapy would be the correction of this deficit. Succinate supplementation in the diet of TNF ∆ARE/+ mice, which spontaneously developed a Crohn's disease-like ileitis, resulted in less injury and reduced inflammation [13].…”