富含植物性 DHA 及等量 AA 对六周龄易过敏 BALB/c 幼鼠免疫系统和口腔耐受形成的编程作用。
The Programming Effect of Plant-Based DHA, Along with Equivalent AA, on Immune System and Oral Tolerance Development in Six-Week Allergy Prone BALB/c Pups.
机构信息
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
出版信息
J Nutr. 2023 Aug;153(8):2482-2496. doi: 10.1016/j.tjnut.2023.06.002. Epub 2023 Jun 3.
BACKGROUND
Docosahexaenoic acid (DHA) and arachidonic acid (AA) on oral tolerance (OT) development in allergy-prone infants is less known.
OBJECTIVES
We aim to determine the effects of early life DHA supplementation (1% of total fat, from novel canola oil), along with AA, on OT toward ovalbumin (ova, egg protein) in allergy-prone BALB/c pups at 6-wk.
METHODS
Breastfeeding dams (n ≥ 10/diet) were fed DHA+AA (1% DHA, 1% AA wt/wt of total fat) or control (0% DHA, 0% AA) suckling period diet (SPD) during which pups consumed dam's milk. At 3-wk, pups from each SPD group were assigned to either the control or DHA+AA weaning diet. For OT, pups from each diet group were either orally fed ova or placebo daily from 21-25 d. Systemic immunization to ova was induced through intraperitoneal injections before euthanizing 6-wk pups. Ova-specific immunoglobulin (ova-Ig) and splenocytes ex-vivo cytokine response to different stimuli were analyzed using a 3-factor analysis of variance.
RESULTS
OT-induced suppression was seen in ova-stimulated splenocyte ex-vivo response, where ova-tolerized pups showed significantly lower total immunoglobulin (Ig)G, IgG1, interleukin (IL)-2 and IL-6 production than sucrose (placebo) pups. DHA+AA SPD was associated with 3 times lower plasma concentrations of ova-IgE (P = 0.03) than controls. DHA+AA weaning diet resulted in lower T helper type-2 cytokines (IL-4 and IL-6) with ova stimulation than controls, which may benefit OT. DHA+AA SPD resulted in significantly higher T cell cytokine response [IL-2, interferon-gamma, (IFNγ) and IL-1β] to anti-CD3/CD28 stimulation than controls. The splenocytes stimulated with lipopolysaccharide produced lower inflammatory cytokines (IFNγ, tumor necrosis factor-alpha, IL-6, and C-X-C motif ligand 1), which may be because of lower CD11b+CD68+ splenocytes proportion in pups from DHA+AA SPD than control (all P < 0.05).
CONCLUSIONS
DHA and AA in early life may influence OT in allergy-prone BALB/c mouse offspring, as they effectively promote T helper type-1 immune responses.
背景
二十二碳六烯酸（DHA）和花生四烯酸（AA）对过敏倾向婴儿口服耐受（OT）的发展知之甚少。
目的
我们旨在确定早期生活中 DHA 补充（占总脂肪的 1%，来自新型菜籽油）以及 AA 对过敏倾向 BALB/c 幼崽 6 周时对卵清蛋白（ova，鸡蛋蛋白）OT 的影响。
方法
哺乳母鼠（n≥10/饮食）在哺乳期饮食（SPD）中摄入 DHA+AA（1%DHA，1%AA 占总脂肪的重量/重量）或对照（0%DHA，0%AA），在此期间幼崽摄入母鼠的乳汁。在 3 周时，每个 SPD 组的幼崽被分配到对照组或 DHA+AA 断奶饮食组。对于 OT，来自每个饮食组的幼崽每天从 21-25 天口服给予 ova 或安慰剂。在处死 6 周大的幼崽之前，通过腹腔内注射对 ova 进行全身免疫接种。使用三因素方差分析分析卵清蛋白特异性免疫球蛋白（ova-Ig）和脾细胞体外对不同刺激物的细胞因子反应。
结果
OVA 刺激的脾细胞体外反应中观察到 OT 诱导的抑制，在卵清蛋白耐受的幼崽中，总免疫球蛋白（Ig）G、IgG1、白细胞介素（IL）-2 和 IL-6 的产生明显低于蔗糖（安慰剂）幼崽。DHA+AA SPD 与对照相比，血浆中 ova-IgE 的浓度低 3 倍（P=0.03）。DHA+AA 断奶饮食导致 ova 刺激时辅助性 T 细胞 2 型细胞因子（IL-4 和 IL-6）低于对照，这可能有利于 OT。DHA+AA SPD 导致 CD3/CD28 刺激时 T 细胞细胞因子反应[白细胞介素-2（IL-2）、干扰素-γ（IFNγ）和白细胞介素-1β]显著高于对照。用脂多糖刺激的脾细胞产生较低的炎症细胞因子（IFNγ、肿瘤坏死因子-α、IL-6 和 C-X-C 基序配体 1），这可能是因为 DHA+AA SPD 中的幼崽中 CD11b+CD68+脾细胞比例低于对照（所有 P<0.05）。
结论
生命早期的 DHA 和 AA 可能影响过敏倾向 BALB/c 小鼠后代的 OT，因为它们有效地促进了辅助性 T 细胞 1 型免疫反应。
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