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

International Journal of Molecular Sciences

卷:22

Akihiko Inaba¹  Ken Iwatsuki¹  Ayane Arinaga¹  Takumi Yamane¹  Yuichi Oishi¹  Keisuke Tanaka²  Hiroo Imai³  Takaho Endo⁴  Yasushi Okazaki⁴  Norihito Hayatsu⁴ 

[1] Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 156-8502, Japan;

[2] Genome Research Center, Tokyo University of Agriculture, Tokyo 156-8502, Japan;

[3] Molecular Biology Section, Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University, Kyoto 484-8506, Japan;

[4] RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan;

关键词: tuft cell;    acetylcholine;    intestine;    organoid;    primate;    IL-4;   

DOI  :  10.3390/ijms22157921

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown