Gu Junxiang, Ma Yixian, Chang Qing, Chen Ling
Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.
Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.
Front Immunol. 2025 May 20;16:1600673. doi: 10.3389/fimmu.2025.1600673. eCollection 2025.
Programmed death ligand 1 (PD-L1) is a potential target for autoimmune disease therapies. The gut microbiota plays a critical role in autoimmunity, and may influence therapeutic outcomes of immune therapies in cancer. However, the relationship between PD-L1 and gut microbiota in autoimmune conditions remains unclear. This study aims to investigate the effect of PD-L1 knockout on gut microbiota in an experimental autoimmune uveitis (EAU) model.
EAU was induced via immunization with interphotoreceptor retinoid-binding protein peptide 651-670 (IRBP651-670) in either wild type (WT) or PD-L1 knockout (KO) C57BL/6J female mice. Sham adjuvant was administered to WT or PD-L1 KO mice as healthy controls. The severity of EAU was evaluated through clinical evaluation and histopathological gradings. The characteristics of gut microbiota was analyzed using metagenomic sequencing.
Each group consisted of three biological replicates. The clinical and histopathological scores of EAU were significantly higher in KO_EAU mice than in WT_EAU mice. WT_EAU mice exhibited lower microbial richness than their healthy controls (WT mice), while PD-L1 KO in EAU mice (KO_EAU group) led to increased richness when compared to wild type EAU mice (WT_EAU group). EAU induced a reduction in the abundance of and an increased in sp. PD-L1 knockout in EAU led to an increased abundance of families Bacteroidaceae, Lachnospiraceae and Ruminococcaceae. EAU was associated with declining microbial tryptophan metabolism and up-regulated functions related to lipid and carbohydrate metabolism; PD-L1 knockout in EAU further increased the metabolism of glycan and biosynthesis of 3-deoxy-α-D-manno-2-octulosonate (Kdo), a key component of bacterial lipopolysaccharide (LPS).
Both EAU and PD-L1 knockout modulate gut microbiota, affecting microbial composition - particularly , , Bacteroidaceae, Lachnospiraceae and Ruminococcaceae - and microbial functions such as lipid, carbohydrate and glycan metabolism.
程序性死亡配体1（PD-L1）是自身免疫性疾病治疗的潜在靶点。肠道微生物群在自身免疫中起关键作用，并可能影响癌症免疫治疗的疗效。然而，在自身免疫性疾病中，PD-L1与肠道微生物群之间的关系仍不清楚。本研究旨在探讨PD-L1基因敲除对实验性自身免疫性葡萄膜炎（EAU）模型中肠道微生物群的影响。
通过用视网膜色素上皮结合蛋白肽651-670（IRBP651-670）免疫野生型（WT）或PD-L1基因敲除（KO）的C57BL/6J雌性小鼠诱导EAU。给WT或PD-L1基因敲除小鼠注射假佐剂作为健康对照。通过临床评估和组织病理学分级评估EAU的严重程度。使用宏基因组测序分析肠道微生物群的特征。
每组包括三个生物学重复。KO_EAU小鼠的EAU临床和组织病理学评分显著高于WT_EAU小鼠。WT_EAU小鼠的微生物丰富度低于其健康对照（WT小鼠），而EAU小鼠中的PD-L1基因敲除（KO_EAU组）与野生型EAU小鼠（WT_EAU组）相比导致丰富度增加。EAU导致 丰度降低和 菌属增加。EAU中的PD-L1基因敲除导致拟杆菌科、毛螺菌科和瘤胃球菌科的丰度增加。EAU与微生物色氨酸代谢下降以及脂质和碳水化合物代谢相关功能上调有关；EAU中的PD-L1基因敲除进一步增加了聚糖代谢和细菌脂多糖（LPS）关键成分3-脱氧-α-D-甘露糖-2-辛酮酸（Kdo）的生物合成。
EAU和PD-L1基因敲除均调节肠道微生物群，影响微生物组成——特别是 、 、拟杆菌科、毛螺菌科和瘤胃球菌科——以及脂质、碳水化合物和聚糖代谢等微生物功能。
