The intestinal mucosal surface is directly exposed to daily fluctuations in food and microbes driven by 24-hour light and feeding cycles. Intestinal epithelial tuft cells are key sentinels that surveil the gut luminal environment, but how these cells are diurnally programmed remains unknown. Here, we show that histone deacetylase 3 (HDAC3) controls tuft cell specification and the diurnal rhythm of its biogenesis, which is regulated by the gut microbiota and feeding schedule. Disruption of epithelial HDAC3 decreases tuft cell numbers, impairing antihelminth immunity and norovirus infection. Mechanistically, HDAC3 functions noncanonically to activate transforming growth factor–β (TGF-β) signaling, which promotes rhythmic expression of Pou2f3 , a lineage-defining transcription factor of tuft cells. Our findings reveal an environmental-epigenetic link that controls the diurnal differentiation of tuft cells and promotes rhythmic mucosal surveillance and immune responses in anticipation of exogenous challenges.

中文翻译：

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HDAC3 整合了 TGF β和微生物线索，在粘膜免疫监测中对簇状细胞生物发生和昼夜节律进行编程


肠道粘膜表面直接暴露在 24 小时光照和进食周期驱动的食物和微生物的日常波动中。肠上皮簇状细胞是监视肠道管腔环境的关键哨兵，但这些细胞是如何进行昼夜编程的仍然未知。在这里，我们表明组蛋白脱乙酰酶 3 （HDAC3） 控制簇状细胞规格及其生物发生的昼夜节律，这受肠道微生物群和摄食时间表的调节。上皮 HDAC3 的破坏会减少簇状细胞的数量，损害驱虫免疫和诺如病毒感染。从机制上讲，HDAC3 以非经典方式激活转化生长因子-β （TGF-β） 信号传导，从而促进 Pou2f3 的节律性表达，Pou2f3 是簇状细胞的谱系定义转录因子。我们的研究结果揭示了环境-表观遗传学联系，它控制着簇状细胞的昼夜分化，并促进有节奏的粘膜监测和免疫反应，以应对外源性挑战。