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来自Bifidobacterium longum亚种的甲基化和非甲基化CpG ODN的剂量反应研究. 用于优化Treg细胞刺激的婴儿药

Dongmei Li¹, Idalia Cruz², Sharareh Sorkhabi¹

¹From the Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, D.C.

Allergy and asthma proceedings

|February 26, 2025

概括

来自Bifidobacterium longum的甲基化DNA基因显示出对过敏原免疫疗法 (AIT) 的希望,通过有效诱导调节性T细胞 (Tregs). 最佳Treg诱导需要特定的剂量,突出了对过敏性疾病的潜在治疗应用.

科学领域:

免疫学和过敏学研究研究
微生物DNA治疗方法
监管T细胞诱导的规则

背景情况:

过敏原免疫疗法 (AIT) 旨在诱导调节性T细胞 (Tregs) 在过敏性疾病中长期耐受.
之前的研究表明,来自Bifidobacterium longum的甲基化DNA oligodeoxynucleotides (ODNs) 诱导Tregs,与非甲基化版本不同.
优化Treg活动是提高AIT疗效的关键.

研究的目的:

研究来自B. longum的甲基化和非甲基化DNA基因对炎症和Treg诱导的影响.
为了确定甲基化酸 - 氨酸 (CpG) ODNs的剂量反应关系,以在潜在的临床应用中获得最佳的Treg刺激.

主要方法:

在BALB/c小鼠中,通过不同的剂量计划 (单次100μg,四次25μg或多次100μg剂量) 给予分级剂量的甲基化或非甲基化ODN.
使用ELISA测量IL-17A,IL-4,IL-10和TGF-β的血清水平.
脊髓Treg群体 (CD25+FOXP3+) 通过流动细胞计量进行评估.

主要成果:

与非甲基化ODN和对照组相比,甲基化ODN显著增加了CD25+FOXP3+Tregs.
一次100微克剂量 (A计划) 有效诱导Tregs,由IL-10水平升高证明.
多次低剂量 (B计划) 不能激活Tregs,多次高剂量 (C计划) 减少Treg反应,表明临界剂量值.

结论:

来自B. longum的甲基化DNA基因在AIT中显示出作为治疗剂的巨大潜力.
已建立的甲基化CpGODN的剂量反应关系为针对过敏性疾病中Treg活性的临床应用提供了基础.

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