Howitt Michael R, Cao Y Grace, Gologorsky Matthew B, Li Jessica A, Haber Adam L, Biton Moshe, Lang Jessica, Michaud Monia, Regev Aviv, Garrett Wendy S
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115;
Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115.
Immunohorizons. 2020 Jan 24;4(1):23-32. doi: 10.4049/immunohorizons.1900099.
Tuft cells are an epithelial cell type critical for initiating type 2 immune responses to parasites and protozoa in the small intestine. To respond to these stimuli, intestinal tuft cells use taste chemosensory signaling pathways, but the role of taste receptors in type 2 immunity is poorly understood. In this study, we show that the taste receptor TAS1R3, which detects sweet and umami in the tongue, also regulates tuft cell responses in the distal small intestine. BALB/c mice, which have an inactive form of TAS1R3, as well as -deficient C57BL6/J mice both have severely impaired responses to tuft cell-inducing signals in the ileum, including the protozoa and succinate. In contrast, TAS1R3 is not required to mount an immune response to the helminth , which infects the proximal small intestine. Examination of uninfected mice revealed a modest reduction in the number of tuft cells in the proximal small intestine but a severe decrease in the distal small intestine at homeostasis. Together, these results suggest that TAS1R3 influences intestinal immunity by shaping the epithelial cell landscape at steady-state.
簇状细胞是一种上皮细胞类型，对于在小肠中启动针对寄生虫和原生动物的2型免疫反应至关重要。为了对这些刺激做出反应，肠道簇状细胞利用味觉化学感应信号通路，但味觉受体在2型免疫中的作用尚不清楚。在这项研究中，我们表明，在舌中检测甜味和鲜味的味觉受体TAS1R3，也调节远端小肠中的簇状细胞反应。具有无活性形式TAS1R3的BALB/c小鼠以及缺乏该受体的C57BL6/J小鼠，对回肠中诱导簇状细胞的信号（包括原生动物和琥珀酸盐）的反应均严重受损。相比之下，对感染近端小肠的蠕虫进行免疫反应则不需要TAS1R3。对未感染的小鼠进行检查发现，近端小肠中簇状细胞数量略有减少，但在稳态时远端小肠中簇状细胞数量严重减少。总之，这些结果表明，TAS1R3通过在稳态时塑造上皮细胞格局来影响肠道免疫。
