中国肿瘤生物治疗杂志2025，Vol.32Issue(12)：1228-1235,8.DOI:10.3872/j.issn.1007-385x.2025.12.003
2'-岩藻糖基乳糖缓解小鼠免疫检查点抑制剂相关结肠炎的机制研究
Mechanistic study on the effects of 2'-fucosyllactose in alleviating immune checkpoint inhibitor-induced colitis in mice
摘要
Abstract
Objective:To investigate the effect of 2'-fucosyllactose(2'-FL)on immune checkpoint inhibitor-induced colitis(ICIC)in mice and its possible mechanisms.Methods:BALB/c mice were randomly assigned into the normal control(NC)group,dextran sulfate sodium(DSS)group,ICIC group,and ICIC+2'-FL group,using a random number table method.Mice in the DSS group were provided with 3.5%DSS-containing drinking water for seven days to induce colonic inflammation.The ICIC group was intraperitoneally injected of cytotoxic T lymphocyte-associated antigen 4(CTLA-4;dose:150 µg)on day 0 and day 4,while simultaneously consuming 3.5%DSS-containing drinking water.The ICIC+2'-FL group received daily intragastric administration of 2'-FL(150 mg/[kg·d])concurrently with the establishment of ICIC model.Changes in body weight and disease activity index(DAI)were statistically analyzed.On day 7,all mice were sacrificed,and the colon length was measured.Hematoxylin and eosin(H&E)staining was performed to observe histomorphological changes in colon tissues across groups.Immunohistochemistry(IHC)was conducted to assess the infiltration of CD3+T cells and CD19+B cells in colonic tissues.RNA sequencing(RNA-seq)was performed on colon tissues.The differentially expressed genes(DEGs)were subjected to Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Results:Compared with the NC and DSS groups,the ICIC group showed significant body weight loss,elevated DAI scores,and shorter colon length(all P<0.05);besides,the colon mucosal integrity was damaged,with typical ulcerative lesions.Compared with the ICIC group,ICIC+2'-FL group demonstrated significantly alleviated body weight loss,reduced DAI score,and restored colon length(all P<0.05).Transcriptomic results revealed 51 DEGs in the ICIC+2'-FL group(vs ICIC group).GO functional annotation and KEGG enrichment analysis suggested that the protective effect of 2'-FL against ICIC-like symptoms might be associated with upregulation of signaling pathways related to B cell receptor,B cell proliferation regulation,inflammatory responses,and tissue repair.Conclusion:Human milk oligosaccharide 2'-FL significantly alleviates the pathological progression of ICIC by modulating B-cell receptor-related signaling pathways and pathways associated with inflammation responses and tissue repair,thereby reducing colonic damage in ICIC mice.关键词
免疫检查点抑制剂相关结肠炎/2'-岩藻糖基乳糖/转录组测序/人乳寡糖/结肠炎Key words
immune checkpoint inhibitor-induced colitis(ICIC)/2'-fucosyllactose(2'-FL)/transcriptome sequencing/human milk oligosaccharide(HMO)/colitis分类
医药卫生引用本文复制引用
莫锦灵,张洪涛,胡楠,周栋,朱傲霜,蒋敬庭,张雯婷..2'-岩藻糖基乳糖缓解小鼠免疫检查点抑制剂相关结肠炎的机制研究[J].中国肿瘤生物治疗杂志,2025,32(12):1228-1235,8.基金项目
中国博士后科研基金(No.2021M700546) （No.2021M700546）
江苏省卫健委科研课题(No.MQ2024030) （No.MQ2024030）
常州市科技计划项目(No.CJ20245049 （）
No.CE20235066) （）
南京医科大学常州医学中心重点项目(No.CMCM202314) （No.CMCM202314）
南通大学临床专项(No.2023LY027) （No.2023LY027）
