Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
J Nutr. 2022 Sep 6;152(9):2165-2178. doi: 10.1093/jn/nxac118.
A T helper type-2 (Th2) skewed immune response is associated with food allergies. DHA and arachidonic acid (ARA) have been shown to promote oral tolerance (OT) in healthy rodents.
We studied the effect of combined ARA + DHA supplementation during the suckling and weaning periods on OT and immune system development in Th2-skewed Brown Norway rat offspring.
Dams were fed ARA + DHA (0.45% ARA, 0.8% DHA wt/wt of total fat; n = 10) as a suckling period diet (SPD) or control SPD (0% ARA, 0% DHA, n = 8). At 3 wk, offspring from each SPD group received ARA + DHA (0.5% ARA, 0.5% DHA wt/wt of total fat) weaning diet (WD), or control until 8 wk. For OT, offspring were orally exposed to either ovalbumin (OVA) or placebo between 21 and 25 d, followed by systemic immunization with OVA + adjuvant at 7 wk. Primary outcomes, ex vivo cytokine production by splenocytes and plasma OVA-specific Igs, were analyzed using a 3-way ANOVA.
At 8 wk, despite no lasting effect of SPD on splenocytes fatty acids, ARA + DHA WD resulted in 2× higher DHA in splenocyte phospholipid compositions without affecting ARA. OT development was observed in OVA-exposed groups with 15% lower plasma OVA-IgE (P = 0.04) and 35% lower OVA-IgG1 (P = 0.01) than placebo. ARA + DHA SPD resulted in 35% lower OVA-IgG1 and iIL-6 (P = 0.04) when stimulated with LPS, and a higher proportion of mature B cells (OX12+, P = 0.0004, and IgG+, P = 0.008). ARA + DHA WD resulted in 20% higher Th1 cytokines (TNF-α and IFN-γ) production to lymphocyte stimulant and higher splenocyte proportion of CD45RA+ (pan-B cells) and OX6+ (dendritic cells) than control WD (P values < 0.05).
Combined supplementation of ARA and DHA is beneficial for OT development, especially in the suckling period. Further, ARA + DHA supplementation can also counteract the Th2-skewed immunity of Brown Norway rat offspring through higher Th1 cytokine production by lymphocytes.
辅助性 T 细胞 2 型（Th2）偏倚的免疫反应与食物过敏有关。已经表明，二十二碳六烯酸（DHA）和花生四烯酸（ARA）可促进健康啮齿动物的口服耐受（OT）。
我们研究了在哺乳期和断奶期同时补充 ARA+DHA 对 Th2 偏倚的褐家鼠后代 OT 和免疫系统发育的影响。
母鼠在哺乳期（SPD）时喂食 ARA+DHA（0.45%ARA，0.8%DHA wt/wt 总脂肪；n=10）或对照 SPD（0%ARA，0%DHA，n=8）。在 3 周龄时，每个 SPD 组的后代接受 ARA+DHA（0.5%ARA，0.5%DHA wt/wt 总脂肪）断奶期饮食（WD）或对照 WD 直至 8 周龄。为了进行 OT，在 21 至 25 天期间，后代口服暴露于卵清蛋白（OVA）或安慰剂，然后在 7 周时用 OVA 和佐剂进行全身免疫接种。使用三因素方差分析分析脾细胞体外细胞因子产生和血浆 OVA 特异性 Ig 的主要结局。
在 8 周龄时，尽管 SPD 对脾细胞脂肪酸没有持久影响，但 ARA+DHA WD 导致脾细胞磷脂组成中 DHA 增加 2 倍，而 ARA 没有变化。在接受 OVA 暴露的组中观察到 OT 发育，与安慰剂相比，血浆 OVA-IgE 降低 15%（P=0.04），OVA-IgG1 降低 35%（P=0.01）。与 LPS 刺激相比，ARA+DHA SPD 导致 OVA-IgG1 和 iIL-6 降低 35%（P=0.04），并且成熟 B 细胞的比例更高（OX12+，P=0.0004，和 IgG+，P=0.008）。与对照 WD 相比，ARA+DHA WD 导致淋巴细胞刺激产生的 Th1 细胞因子（TNF-α和 IFN-γ）增加 20%，并且脾细胞中 CD45RA+（全 B 细胞）和 OX6+（树突状细胞）的比例更高（P 值均<0.05）。
ARA 和 DHA 的联合补充有利于 OT 发育，尤其是在哺乳期。此外，ARA+DHA 补充还可以通过增加淋巴细胞产生 Th1 细胞因子来对抗褐家鼠后代的 Th2 偏倚免疫。
