α-亚麻酸通过 IL-4Rα-JAK2-STAT3 通路抑制 CD4+ T 细胞分化，改善过敏性鼻炎患者鼻粘膜上皮屏障功能,Phytomedicine

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α-亚麻酸通过 IL-4Rα-JAK2-STAT3 通路抑制 CD4+ T 细胞分化，改善过敏性鼻炎患者鼻粘膜上皮屏障功能
Phytomedicine ( IF 6.7 ) Pub Date : 2023-04-21 , DOI: 10.1016/j.phymed.2023.154825
Yuanyuan Ding ₁ , Yuejin Wang ₁ , Yonghui Zhang ₁ , Baowen Dang ₁ , Shiting Hu ₁ , Chenrui Zhao ₁ , Yihan Huang ₁ , Guodong Zheng ₁ , Tianyou Ma ₂ , Tao Zhang ₁

Affiliation

背景

过敏性鼻炎 (AR) 定义为特应性个体接触过敏原后鼻粘膜的炎症和组织重塑。α-亚麻酸 [cis-9, cis-12, cis-15-octadecatrienoic acid (18:3)] (ALA) 作为膳食补充剂可以减轻炎症和过敏症状。

客观的

评估ALA在AR小鼠模型中的潜在治疗作用和机制。

方法

卵清蛋白致敏的 AR 小鼠模型接受口服 ALA 给药的挑战。研究了鼻部症状、组织病理学、免疫细胞浸润和杯状细胞增生。通过 ELISA 测定血清和鼻液中 IgE、TNF-β、IFN-γ、IL-2、IL-4、IL-5、IL-12、IL-13 和 IL-25 的水平。对 occludin 和 zonula occludens-1 表达进行定量 RT-PCR 和免疫荧光。从外周血和脾脏淋巴细胞中分离出CD3 ⁺ CD4 ⁺ T -细胞，并测定 Th1/Th2 比率。分离小鼠幼稚 CD4 ⁺ T 细胞并测定 Th1/Th2 比率、IL-4Rα 表达和 IL5/IL13 分泌。AR 小鼠的 IL-4Rα-JAK2-STAT3 通路变化通过蛋白质印迹进行。

结果

卵清蛋白诱导 AR、鼻部症状、病理表现、IgE 和细胞因子产生。ALA 处理的小鼠表现出鼻部症状减轻、鼻部炎症、鼻中隔增厚、杯状细胞增生和嗜酸性粒细胞浸润。在卵清蛋白攻击小鼠的血清和鼻液中，ALA 降低了 IgE、IL-4 水平，并增加了 Th2 细胞。ALA 阻止了卵清蛋白攻击的 AR 小鼠上皮细胞屏障的破坏。同时，ALA 可防止 IL-4 诱导的屏障破坏。^{ALA通过影响CD4 +} T细胞的分化阶段和阻断IL-4Rα-JAK2-STAT3通路来治疗AR。

结论

本研究表明ALA对卵清蛋白诱导的AR具有潜在的治疗作用。^{ALA可通过IL-4Rα-JAK2-STAT3通路影响CD4 +} T细胞的分化阶段，改善上皮屏障功能。

临床意义

ALA 可能被认为是通过 AR 中 Th1/Th2 比率恢复来改善上皮屏障功能的候选药物。

"点击查看英文标题和摘要"

Alpha-linolenic acid improves nasal mucosa epithelial barrier function in allergic rhinitis by arresting CD4+ T cell differentiation via IL-4Rα-JAK2-STAT3 pathway

Background

Allergic rhinitis (AR) defined as inflammation and tissue remodeling of the nasal mucosa in atopic individuals after allergen exposure. Alpha-linolenic acid [cis-9, cis-12, cis-15-octadecatrienoic acid (18:3)] (ALA) as dietary supplementation can reduce inflammation and allergic symptoms.

Objective

To evaluate the potential therapeutic effect and mechanism of ALA in AR mouse model.

Methods

Ovalbumin sensitized AR mouse model were challenged with oral ALA administration. Nasal symptoms, tissue pathology, immune cell infiltration and goblet cell hyperplasia were investigated. Levels of IgE, TNF-β, IFN-γ, IL-2, IL-4, IL-5, IL-12, IL-13 and IL-25 were determined by ELISA in serum and nasal fluid. Quantitative RT-PCR and immunofluorescence were performed for occludin and zonula occludens-1 expression. CD3⁺CD4⁺ T-cells from peripheral blood and splenic lymphocytes were isolated and Th1/Th2 ratio were determined. Mouse naive CD4⁺ T cell were isolated and Th1/Th2 ratio, IL-4Rα expression, and IL5/IL13 secretion were determined. IL-4Rα-JAK2-STAT3 pathway change in AR mice were performed by western blot.

Results

Ovalbumin induced AR, nasal symptoms, pathological performance, IgE, and cytokine production. ALA treated mice showed reduced nasal symptoms, nasal inflammation, nasal septum thickening, goblet cell hyperplasia, and eosinophil infiltration. In serum and nasal fluid of ovalbumin challenged mice, ALA decreased IgE, IL-4 levels, and the increase of Th2-cells. ALA prevented the disruption of the epithelial cell barrier in ovalbumin-challenged AR mice. Simultaneously, ALA prevents IL-4 induced barrier disruption. ALA treatment of AR by affecting the differentiation stage of CD4⁺T cells and block IL-4Rα-JAK2-STAT3 pathway.

Conclusion

This study suggests that ALA has the potential therapeutic effect to ovalbumin-induced AR. ALA can affect the differentiation stage of CD4⁺T cells and improve epithelial barrier functions through IL-4Rα-JAK2-STAT3 pathways.