Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Front Immunol. 2022 Feb 14;13:822867. doi: 10.3389/fimmu.2022.822867. eCollection 2022.
The interests in intestinal epithelial tuft cells, their basic physiology, involvement in immune responses and relevance for gut diseases, have increased dramatically over the last fifteen years. A key discovery in 2016 of their close connection to helminthic and protozoan infection has further spurred the exploration of these rare chemosensory epithelial cells. Although very sparse in number, tuft cells are now known as important sentinels in the gastrointestinal tract as they monitor intestinal content using succinate as well as sweet and bitter taste receptors. Upon stimulation, tuft cells secrete a broad palette of effector molecules, including interleukin-25, prostaglandin E and D, cysteinyl leukotriene C, acetylcholine, thymic stromal lymphopoietin, and β-endorphins, some of which with immunomodulatory functions. Tuft cells have proven indispensable in anti-helminthic and anti-protozoan immunity. Most studies on tuft cells are based on murine experiments using double cortin-like kinase 1 (DCLK1) as a marker, while human intestinal tuft cells can be identified by their expression of the cyclooxygenase-1 enzyme. So far, only few studies have examined tuft cells in humans and their relation to gut disease. Here, we present an updated view on intestinal epithelial tuft cells, their physiology, immunological hub function, and their involvement in human disease. We close with a discussion on how tuft cells may have potential therapeutic value in a clinical context.
在过去的十五年中，人们对肠上皮簇细胞及其基本生理学、在免疫反应中的作用以及与肠道疾病的相关性的兴趣大大增加。2016 年的一项重要发现是，它们与寄生虫和原生动物感染密切相关，这进一步推动了对这些罕见的化学感觉上皮细胞的探索。尽管簇细胞的数量非常稀少，但它们现在被认为是胃肠道中的重要哨兵，因为它们使用琥珀酸以及甜和苦味觉受体来监测肠道内容物。在受到刺激时，簇细胞会分泌一系列效应分子，包括白细胞介素 25、前列腺素 E 和 D、半胱氨酰白三烯 C、乙酰胆碱、胸腺基质淋巴生成素和β-内啡肽，其中一些具有免疫调节功能。簇细胞在抗寄生虫和抗原生动物免疫中是不可或缺的。大多数关于簇细胞的研究都是基于使用双皮质素样激酶 1（DCLK1）作为标记的小鼠实验进行的，而人类肠道簇细胞可以通过其环氧化酶-1 酶的表达来识别。到目前为止，只有少数研究检查了人类的簇细胞及其与肠道疾病的关系。在这里，我们介绍了对肠上皮簇细胞及其生理学、免疫中枢功能以及它们在人类疾病中的作用的最新观点。最后，我们讨论了簇细胞在临床环境中可能具有的潜在治疗价值。
