Abstract
In the intestine, the innate immune system excludes harmful substances and invading microorganisms. Tuft cells are taste-like chemosensory cells found in the intestinal epithelium involved in the activation of group 2 innate lymphoid cells (ILC2). Although tuft cells in other tissues secrete the neurotransmitter acetylcholine (ACh), their function in the gut remains poorly understood. In this study, we investigated changes in the expression of genes and cell differentiation of the intestinal epithelium by stimulation with interleukin-4 (IL-4) or IL-13 in macaque intestinal organoids. Transcriptome analysis showed that tuft cell marker genes were highly expressed in the IL-4- and IL-13-treated groups compared with the control, and the gene expression of choline acetyltransferase (ChAT), a synthesis enzyme of ACh, was upregulated in IL-4- and IL-13-treated groups. ACh accumulation was observed in IL-4-induced organoids using high-performance liquid chromatography-mass spectrometry (HPLC/MS), and ACh strongly released granules from Paneth cells. This study is the first to demonstrate ACh upregulation by IL-4 induction in primates, suggesting that IL-4 plays a role in Paneth cell granule secretion via paracrine stimulation.
Highlights
The intestinal epithelium is exposed to a variety of chemicals or microorganisms that can be both beneficial and harmful to the body
We propose that ACh secreted by tuft cells acts in a paracrine manner to positively regulate granule secretion from Paneth cells
We tested whether modified media could be used to culture macaque intestinal organoids
Summary
The intestinal epithelium is exposed to a variety of chemicals or microorganisms that can be both beneficial and harmful to the body. To maintain homeostasis, intestinal epithelial cells (IECs) exert multiple sensing mechanisms against nutrients, tastants, microorganisms, and chemicals. The tuft cell (or brush cell) is an atypical epithelial cell-type with a characteristic apical tuft of microvilli, and is found in a variety of organs, including the intestine. Recent studies have shown that intestinal tuft cells activate group 2 innate lymphoid cells (ILC2) by secreting interleukin-25 (IL-25), followed by parasite infection [3,4,5]. Activated ILC2 secretes Th2 cytokines, such as IL-13 and IL-4, and promotes the hyperplasia of both tuft and goblet cells, leading to the mucous secretion and activation of intestinal motility, known as the “weep and sweep” response [5]. Other physiological functions of tuft cells in the gut are proposed for functions such as to sense bitter compounds and succinate that will guide hyperplasia of tuft cells [6,7,8,9]
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