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Article

Interleukin-4 Promotes Tuft Cell Differentiation and Acetylcholine Production in Intestinal Organoids of Non-Human Primate

1
Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 156-8502, Japan
2
Molecular Biology Section, Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University, Kyoto 484-8506, Japan
3
Genome Research Center, Tokyo University of Agriculture, Tokyo 156-8502, Japan
4
RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
*
Authors to whom correspondence should be addressed.
Academic Editors: Kati Juuti-Uusitalo and Keijo Viiri
Int. J. Mol. Sci. 2021, 22(15), 7921; https://doi.org/10.3390/ijms22157921
Received: 1 July 2021 / Revised: 20 July 2021 / Accepted: 21 July 2021 / Published: 24 July 2021
(This article belongs to the Special Issue Novel Biorelevant Intestinal Epithelial In Vitro Models)
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. View Full-Text
Keywords: tuft cell; acetylcholine; intestine; organoid; primate; IL-4 tuft cell; acetylcholine; intestine; organoid; primate; IL-4
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MDPI and ACS Style

Inaba, A.; Arinaga, A.; Tanaka, K.; Endo, T.; Hayatsu, N.; Okazaki, Y.; Yamane, T.; Oishi, Y.; Imai, H.; Iwatsuki, K. Interleukin-4 Promotes Tuft Cell Differentiation and Acetylcholine Production in Intestinal Organoids of Non-Human Primate. Int. J. Mol. Sci. 2021, 22, 7921. https://doi.org/10.3390/ijms22157921

AMA Style

Inaba A, Arinaga A, Tanaka K, Endo T, Hayatsu N, Okazaki Y, Yamane T, Oishi Y, Imai H, Iwatsuki K. Interleukin-4 Promotes Tuft Cell Differentiation and Acetylcholine Production in Intestinal Organoids of Non-Human Primate. International Journal of Molecular Sciences. 2021; 22(15):7921. https://doi.org/10.3390/ijms22157921

Chicago/Turabian Style

Inaba, Akihiko, Ayane Arinaga, Keisuke Tanaka, Takaho Endo, Norihito Hayatsu, Yasushi Okazaki, Takumi Yamane, Yuichi Oishi, Hiroo Imai, and Ken Iwatsuki. 2021. "Interleukin-4 Promotes Tuft Cell Differentiation and Acetylcholine Production in Intestinal Organoids of Non-Human Primate" International Journal of Molecular Sciences 22, no. 15: 7921. https://doi.org/10.3390/ijms22157921

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