gd T-cells regulate transcriptional response to diet in the intestinal epithelium. gd T-cells regulate transcriptional response to diet in the intestinal epithelium

As a site of direct encounter with the external environment, the intestine must balance nutrient uptake with barrier defense. This requires coordination between numerous cell types that engage whole tissue responses to changes in environmental variables. To investigate how nutrient uptake is regulated in the small intestine, we tested the effects of diets with different macronutrient composition on epithelial cell gene expression. We found that expression of enzymes and transporters required for digestion and absorption of carbohydrates, but not protein, was dependent on substrate availability. Surprisingly, the ‘on-demand’ induction of this machinery required gd Tcells, which regulated this program via suppression of IL-22 expression by ILC3s. We found that nutrient availability alters the tissue localization and transcriptome of gd T-cells and that transcriptional responses to diet involved cellular remodeling of the epithelial compartment. This work thus identified a novel role of intestinal gd T-cells in nutrient sensing. Overall design: Bulk RNA-seq of intestinal epithelial cells, gd T cells, and ab T cells from mice fed with high carb or high protein diet, respectively.

作为与外部环境直接接触的组织位点，肠道必须在营养摄取与屏障防御之间维持动态平衡。这一生理过程需要多种细胞类型协同配合，以介导整体组织对环境变量变化的应答反应。为探究小肠内营养摄取的调控机制，我们分析了不同宏量营养素组成的膳食对上皮细胞基因表达的影响。研究发现，碳水化合物（而非蛋白质）消化与吸收所需的酶及转运蛋白的表达，依赖于底物的可获得性。令人意外的是，该消化吸收相关功能系统的“按需”诱导依赖于γδ T细胞（gd T cells），后者通过抑制3型固有淋巴细胞（ILC3s）的IL-22表达来调控这一转录程序。我们进一步发现，营养可获得性会改变肠道γδ T细胞的组织定位与转录组特征，而机体对膳食的转录应答涉及上皮区室的细胞重塑。因此本研究揭示了肠道γδ T细胞在营养感知中的全新功能。实验设计：分别对喂食高碳水膳食或高蛋白膳食的小鼠的肠道上皮细胞、γδ T细胞（gd T cells）以及αβ T细胞（ab T cells）进行批量RNA测序（Bulk RNA-seq）。