Recently identified regulatory PMN control immune-driven dry eye disease (DED) in females by producing the arachidonic acid (ω-6)-derived specialized pro-resolving mediator (SPM), LXA₄, in lymph nodes. Dietary ω-3 docosahexaenoic acid (DHA) is protective in DED but mechanisms of action remain elusive. DHA is converted to ω-3 SPMs by PMN via the same lipoxygenases (LOX) that generate LXA₄. We investigated if dietary DHA amplifies SPM formation and affects T effector cell function and/or regulatory PMN in DED. DED was induced in mice on a DHA-enriched or ω-3-deficient diet. DHA deficiency amplified DED with marked sex-specific differences. Dietary DHA protection against dry eye disease correlated with increased PMN levels in lymph nodes, ocular tissues, and unexpectedly, selective amplification of LXA₄ tissue levels. Dietary DHA increased 12/15-LOX and decreased 5-LOX expression in lymph nodes and isolated lymph node PMN, which correlated with amplified LXA₄ formation. Acute DHA treatment rescued DHA-deficient females from exaggerated DED by amplifying lymph node LXA₄ formation, increasing T_reg and decreasing T_H1 and T_H17 effector cells. Our results identify DHA regulation of LXA₄ producing PMN in ocular tissues and lymph nodes in health and immune disease as novel mechanism and determinant for T-cell responses to routine ocular injury or stress signals.

中文翻译：

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膳食 DHA 可放大组织和淋巴结 PMN 中的 LXA4 回路，对免疫驱动的干眼病具有保护作用。

最近发现调节性 PMN 通过在淋巴结中产生花生四烯酸 (ω-6) 衍生的专门促分解介质 (SPM)、LXA ₄来控制女性免疫驱动的干眼病 (DED) 。膳食 ω-3 二十二碳六烯酸 (DHA) 在 DED 中具有保护作用，但作用机制仍不清楚。DHA 通过产生 LXA _{4的相同脂氧合酶 (LOX) 被 PMN 转化为 ω-3 SPM}. 我们研究了饮食中的 DHA 是否会放大 SPM 的形成并影响 DED 中的 T 效应细胞功能和/或调节性 PMN。在富含 DHA 或缺乏 ω-3 的饮食的小鼠中诱导 DED。DHA 缺乏会放大 DED，并具有明显的性别差异。膳食 DHA 对干眼病的保护作用与淋巴结、眼组织中 PMN 水平的增加相关，并且意外地与 LXA ₄组织水平的选择性扩增相关。膳食 DHA 增加淋巴结和孤立淋巴结 PMN 中的 12/15-LOX 并降低 5-LOX 表达，这与放大的 LXA ₄形成相关。急性 DHA 治疗通过扩大淋巴结 LXA ₄形成、增加 T _reg和降低 T_H 1 和 T _H 17 效应细胞。我们的结果确定 DHA 对健康和免疫疾病中眼组织和淋巴结中产生 PMN的 LXA _{4的调节是 T 细胞对常规眼损伤或应激信号作出反应的新机制和决定因素。}