沃尔特和伊丽莎·霍尔医学研究所Cyril Seillet小组近日取得一项新成果。经过不懈努力，他们提出了急性暴露于高脂肪饮食会损害ILC3功能和肠道稳态。相关论文于2025年4月14日发表在《免疫学》杂志上。

该研究团队发现，在48小时内，HFD会损害肠道3组先天淋巴样细胞（ILC3s）及其产生白细胞介素-22（IL-22）的能力，而白细胞介素-22是维持肠道稳态的关键。这种功能丧失与快速生态失调、肠道通透性增加、抗菌肽、黏液和紧密连接蛋白的产生减少有关。饱和脂肪酸通过氧化代谢破坏ILC3功能，而不饱和脂肪酸通过形成脂滴使二酰基甘油O-酰基转移酶（DGAT）酶保持ILC3分泌IL-22。在炎症发生时，饱和脂肪酸会破坏ILC3s产生IL-22，并增加肠道对损伤的易感性。他们的研究结果揭示了饱和脂肪酸和不饱和脂肪酸通过不同的ILC3s代谢途径对肠道内稳态的不同急性影响。

据悉，长期暴露于高脂肪饮食（HFD）会加剧肠道疾病病理，但肠道炎症发展之前的早期事件仍然知之甚少。

附：英文原文

Title: Acute exposure to high-fat diet impairs ILC3 functions and gut homeostasis

Author: Le Xiong, Shanti Diwakarla, Roxanne Chatzis, Olivia Artaiz, Matthew Macowan, Shengbo Zhang, Alexandra Garnham, Pooranee K. Morgan, Natalie A. Mellett, Peter J. Meikle, Graeme I. Lancaster, Benjamin J. Marsland, Stephen L. Nutt, Cyril Seillet

Issue&Volume: 2025-04-14

Abstract: Prolonged exposure to a high-fat diet (HFD) exacerbates intestinal disease pathology, yet the early events preceding the development of gut inflammation remain poorly understood. Here, we show that within 48 h, HFD impairs intestinal group 3 innate lymphoid cells (ILC3s) and their capacity to produce interleukin-22 (IL-22), critical for maintaining gut homeostasis. This loss of function was associated with rapid dysbiosis, increased gut permeability, and reduced production of antimicrobial peptides, mucus, and tight-junction proteins. While saturated fatty acids metabolized through oxidation impaired ILC3 function, unsaturated fatty acids sustained IL-22 secretion by ILC3s through the formation of lipid droplets using diacylglycerol O-acyltransferase (DGAT) enzymes. Upon inflammation, saturated fatty acids impaired IL-22 production by ILC3s and increased the susceptibility of the gut to injury. Our findings reveal the differential acute impact of saturated and unsaturated fatty acids on gut homeostasis through distinct metabolic pathways in ILC3s.

DOI: 10.1016/j.immuni.2025.03.017

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00136-0