Mucosal Tuft Cell Density Is Increased in Diarrhea-Predominant Irritable Bowel Syndrome Colonic Biopsies.

Jessica Aigbologa,Maeve Connolly,Dervla O'Malley,Julliette M Buckley

doi:10.3389/fpsyt.2020.00436

Jessica Aigbologa, Maeve Connolly + Show 2 more

Open Access

https://doi.org/10.3389/fpsyt.2020.00436

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Abstract

Tuft cells are rare chemosensory sentinels found in the gut epithelium. When triggered by helminth infection, tuft cells secrete interleukin-25 (IL-25) basolaterally and subsequently evoke an immune response. Irritable bowel syndrome (IBS) is a common and heterogeneous disorder characterized by bowel dysfunction and visceral pain sensitivity. Dysfunctional gut-brain communication and immune activation contribute to the pathophysiology of this disorder. The study aims were to investigate changes in tuft cell density in non-post-infectious IBS patients. Immunofluorescent labeling of DCLK1-positive tuft cells was carried out in mucosal biopsies from the distal colons of diarrhea and constipation-predominant IBS patients and healthy controls. Tuft cell numbers were also assessed in animal models. Concentrations of interleukin-25 (IL-25) secreted from colonic biopsies and in plasma samples were analyzed using an immunoassay. The density of tuft cells was increased in diarrhea—but not constipation-predominant IBS patient colonic biopsies. Biopsy secretions and plasma concentrations of IL-25 were elevated in diarrhea—but not constipation-predominant IBS participants. Tuft cell hyperplasia was detected in a rat model of IBS but not in mice exposed to chronic stress. Tuft cell hyperplasia is an innate immune response to helminth exposure. However, the patients with diarrhea-predominant IBS have not reported any incidents of enteric infection. Moreover, rats exhibiting IBS-like symptoms displayed increased tuft cell density but were not exposed to helminths. Our findings suggest that factors other than helminth exposure or chronic stress lead to tuft cell hyperplasia in IBS colonic biopsies.

Highlights

Tuft cells are rare differentiated epithelial cells, anatomically and functionally distinct from other border cells in the gastrointestinal (GI) tract [1]
Tuft Cell Density Is Elevated in Irritable bowel syndrome (IBS)-D Patient Biopsies
We have examined tuft cell density in colonic mucosal biopsies from patients with IBS, diagnosed in the absence of previous known enteric infection

Summary

Introduction

Tuft cells are rare differentiated epithelial cells, anatomically and functionally distinct from other border cells in the gastrointestinal (GI) tract [1]. Characterized by long, blunt microvilli, pear-shaped tuft cells are scattered along the crypt-villus axis [2]. They express a microtubule linked protein known as Doublecortin Linked Kinase-1 [3] In particular [9], uniquely stimulate release of immune cytokines, such as interleukin (IL)-25 ( known as IL-17E), from tuft cells [10,11,12]. IL-25, in turn, induces secretion of IL-13 from stromal group 2 innate lymphoid cells (ILC2), which promote release of IgE, eosinophilia, goblet cell hyperplasia [13] and, in a feed forward circuit, tuft cell hyperplasia [14]

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