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. 2020;41(2):113-118.
doi: 10.2220/biomedres.41.113.

Distribution of duodenal tuft cells is altered in pediatric patients with acute and chronic enteropathy

Won Jae Huh  1   2 , Joseph Te Roland  1   3 , Masato Asai  4 , Izumi Kaji  1   3
Affiliations

Distribution of duodenal tuft cells is altered in pediatric patients with acute and chronic enteropathy

Won Jae Huh et al. Biomed Res. 2020.

Abstract

Clinical interest into the function of tuft cells in human intestine has increased in recent years. However, no quantitative study has examined intestinal tuft cells in pathological specimens from patients. This study quantified tuft cell density by using a recently identified marker, specific for tyrosine phosphorylation (pY1798) of girdin (also known as CCDC88A or GIV) in the duodenum of pediatric patients. Deidentified sections with pathological diagnosis of acute duodenitis, ulcer, or celiac disease, and age-matched normal control were analyzed under double-blind conditions. Immunostaining for pY1798-girdin demonstrated the distinct shape of tuft cells with and filopodia-like basolateral membrane structure and a small apical area, which densely expressed gamma-actin. As compared to normal tissues, the specimens diagnosed as celiac disease and duodenal ulcer had significantly fewer tuft cell numbers. In contrast, acute duodenitis showed varied population of tuft cells. The mucosa with severe inflammation showed lower tuft cell numbers than the specimens with none to mild inflammation. These results suggest that loss of tuft cells may be involved in prolonged inflammation in the duodenal mucosa and disrupted mucosal integrity. pY1798-girdin and gamma-actin are useful markers for investigating the distribution and morphologies of human intestinal tuft cells under healthy and pathological conditions.

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Figures

Fig. 1
Fig. 1
Identification of duodenal tuft cells. z-stack confocal images of immunoreactivities for pY1798-girdin (pGRDN, a and d) and gamma-actin (ACTG1, b and e) in normal duodenal mucosa. pGRDN staining demonstrates the distinct shape of tuft cells with narrow apical area. Villus tuft cells demonstrate dense and long microvilli that consist of both pGRDN and ACTG1 (asterisk) (a–c). Tuft cells in crypt regions lack the dense gamma-actin structure. Filopodia-like structures are frequently identified in the basal part of tuft cells (arrows) (d–f).
Fig. 2
Fig. 2
Multiplexed immunostaining for pY1798-girdin (pGRDN) and pEGFR in the intestinal tuft cells. After staining with pGRDN antibody (a and c), the antibodies are stripped off, and the absence of fluorescence is conformed (d). The same sections are then stained with pEGFR antibody (b and e). Nuclei are counterstained every round of imaging (c–e, blue). Distribution of these two markers is mostly identical in the villi and crypts, as well as in the microvilli and long basal root-let of tuft cells.
Fig. 3
Fig. 3
Distribution of pY1798-girdin-positive (pGRDN+) tuft cells in duodenal specimens. a–c: Representative images of specimens diagnosed as normal (a), celiac disease (b), and duodenal ulcer (c). Whole-slide images of immunostaining for pGRDN (red), ACTG1 (green), and nuclei (blue) are scanned and analyzed. Compared to normal mucosa, specimens with celiac disease (b) or inflamed mucosa with duodenal ulcer (c) show fewer tuft cells. d: Tuft cell numbers are counted and calculated per mucosal area. *P < 0.05 vs. Normal by Kruskal-Wallis test with uncorrected Dunn’s test. Each datapoint indicates the average for each slide from one patient (n = 8–15 patients), including 1–8 specimens per patient. Bars indicate median of each group.
Fig. 4
Fig. 4
More severe inflammation is associated with tuft cell loss in specimens with duodenitis and/or ulcer. pGRDN+ cell numbers per mucosal area are calculated in duodenal biopsies with mild, moderate, or severe inflammation, and compared to that in not inflamed specimens (same as normal in Fig. 3). Each datapoint indicates the value of each slide from one patient (n = 5–15), and the bars indicate median of each group. *P < 0.05 by Kruskal-Wallis test with uncorrected Dunn’s test.
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