Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
Science. 2021 Mar 19;371(6535). doi: 10.1126/science.aba8310.
The intestine is a site of direct encounter with the external environment and must consequently balance barrier defense with nutrient uptake. To investigate how nutrient uptake is regulated in the small intestine, we tested the effect of diets with different macronutrient compositions on epithelial gene expression. We found that enzymes and transporters required for carbohydrate digestion and absorption were regulated by carbohydrate availability. The "on-demand" induction of this machinery required γδ T cells, which regulated this program through the suppression of interleukin-22 production by type 3 innate lymphoid cells. Nutrient availability altered the tissue localization and transcriptome of γδ T cells. Additionally, transcriptional responses to diet involved cellular remodeling of the epithelial compartment. Thus, this work identifies a role for γδ T cells in nutrient sensing.
肠道是与外部环境直接接触的部位,因此必须在屏障防御和营养吸收之间取得平衡。为了研究小肠中营养吸收是如何调节的,我们测试了不同宏量营养素组成的饮食对上皮基因表达的影响。我们发现,碳水化合物消化和吸收所需的酶和转运体受碳水化合物可用性的调节。这种机制的“按需”诱导需要 γδ T 细胞,γδ T 细胞通过抑制 3 型先天淋巴细胞产生白细胞介素-22 来调节该程序。营养可用性改变了 γδ T 细胞的组织定位和转录组。此外,对饮食的转录反应涉及上皮细胞区室的细胞重塑。因此,这项工作确定了 γδ T 细胞在营养感应中的作用。