Early-life feeding of arachidonic acid and docosahexaenoic acid beneficially modulated ileum and splenocyte oxylipins to support oral tolerance development in allergy-prone BALB/c mice

IF 3

Prostaglandins, leukotrienes, and essential fatty acids Pub Date : 2025-05-23 DOI:10.1016/j.plefa.2025.102689

Ren Wang, Dhruvesh Patel, Susan Goruk, Magaly Rivas Serna, Vera Mazurak, Caroline Richard, Catherine Field

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Abstract

Background

Early-life feeding of arachidonic acid (ARA)+docosahexaenoic acid (DHA) has been shown to promote immune changes associated with oral tolerance (OT). Oxylipins have been demonstrated to be modulated by diet and alter immune function.

Objective

To determine whether early-life feeding of ARA+DHA modulated the ileum and ovalbumin (OVA)-challenged splenocyte oxylipin profile in a way that is beneficial for OT development.

Method

Allergy-prone BALB/c dams were fed a control (0 %ARA, 0 %DHA) or ARA+DHA (1 %ARA, 1 %DHA) diet during suckling. At 3wks, half of the pups were killed to analyze ileum morphology and oxylipin profile. The remaining pups continued consuming the maternal diets. From day 21–25, pups received daily oral gavage of sucrose or OVA, followed by intraperitoneal OVA injections on day 35 and 41. At 6wks, pups were killed to analyze plasma OVA-specific-IgE and -IgG, ileum morphology, splenocyte phospholipid fatty acid composition and ex vivo splenocyte oxylipin production after OVA stimulation.

Results

ARA+DHA supplementation resulted in a 5-fold reduction in plasma OVA-IgE concentration, confirming OT development. At 3wks, ARA+DHA-fed mice had higher ileum levels of 8-HETE, 14,15-DiHETrE, 4-HDHA, 17-HDHA and 19,20-EpDPE and lower levels of 13-HODE and 20-HETE, which suggests better ileum maturation, lower inflammation and enhanced tolerogenic immune regulation to support OT. The longer villi, shorter crypts and higher villus/crypt ratio confirmed the superior ileum maturation. At 6wks, ARA+DHA supplementation increased oxylipin substrates (ARA, DHA, linoleic acid and eicosapentaenoic acid) in splenocyte phospholipids. After OVA stimulation, splenocytes from ARA+DHA-fed mice produced more PGD2, 5-HETE, 15-HETE and 20-HDHA and less TXB2 and 12-HETE, which suggests inhibited Th2 and allergic responses and enhanced tolerogenic immune modulation to support OT.

Conclusion

Early-life feeding of ARA+DHA beneficially modulated the oxylipin profile in the ileum and OVA-challenged splenocytes to support OT development.

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早期喂养花生四烯酸和二十二碳六烯酸有利于调节回肠和脾细胞氧脂，以支持易过敏BALB/c小鼠的口服耐受性发展

幼儿喂养花生四烯酸(ARA)+二十二碳六烯酸（DHA）已被证明可促进与口服耐受性（OT）相关的免疫变化。氧脂素已被证明可以通过饮食调节并改变免疫功能。目的探讨早期喂养ARA+DHA是否能调节回肠和卵清蛋白（OVA）挑战的脾细胞氧脂谱，从而有利于OT的发展。方法在哺乳期给易过敏BALB/c母鼠饲喂对照组（0% ARA, 0% DHA）或ARA+DHA （1% ARA, 1% DHA）饲粮。在3周时，杀死一半的幼崽，分析回肠形态和氧脂质谱。剩下的幼崽继续吃母鼠的食物。第21-25天，每天灌胃蔗糖或卵细胞，第35天和第41天分别腹腔注射卵细胞。6周时，处死幼崽，分析卵细胞刺激后血浆卵细胞特异性ige和igg、回肠形态、脾细胞磷脂脂肪酸组成和体外脾细胞氧脂生成。结果补充sara +DHA导致血浆OVA-IgE浓度降低5倍，证实了OT的发生。在3周时，ARA+ dha喂养的小鼠回肠中8-HETE、14,15- dihetre、4-HDHA、17-HDHA和19,20- epdpe水平较高，13-HODE和20-HETE水平较低，这表明回肠成熟程度更高，炎症程度更低，耐受性免疫调节增强，支持OT。较长的绒毛，较短的隐窝和较高的绒毛/隐窝比证实了上回肠的成熟。在6周时，补充ARA+DHA增加了脾细胞磷脂中的氧化脂质底物（ARA、DHA、亚油酸和二十碳五烯酸）。卵子刺激后，ARA+ dha喂养小鼠脾细胞产生更多的PGD2、5-HETE、15-HETE和20-HDHA，减少TXB2和12-HETE，这表明抑制Th2和过敏反应，增强耐受性免疫调节，支持OT。结论早期喂养ARA+DHA有利于调节回肠和ova刺激的脾细胞中的氧脂质分布，支持OT的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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