Cutaneous immune responses to niacin in photosensitivity

糙皮病是一种光敏综合症，其特征是三个“D”：由于烟酸缺乏而导致的腹泻、皮炎和痴呆。然而，光敏性皮炎的分子机制尚不清楚。在这里，我们表明，用烟酸拮抗剂以及缺乏烟酸的饮食治疗可诱导小鼠光敏性增强，并且用烟酸拮抗剂治疗可诱导严重腹泻伴体重减轻，这表明这是糙皮病模型。有趣的是，烟酸拮抗剂诱导 COX-2 和 PGE 合成 (Ptges) mRNA 表达升高。 COX 抑制剂、Ptges 缺乏或 EP4 受体信号传导阻断可减轻烟酸拮抗剂治疗引起的光敏性。与上述在小鼠中的发现一致，对糙皮病患者皮肤病变的分析证实了 Ptges 表达的增强。总而言之，这些发现表明，烟酸缺乏会导致糙皮病中光敏性的发展，这种光敏性是通过 EP4 信号介导的，以响应 PGE 产量的增加。

Pellagra is a photosensitivity syndrome characterized by three “D’s”: diarrhea, dermatitis and dementia as a result of niacin deficiency. However, the molecular mechanisms of photosensitivity dermatitis underlying the hallmark abnormalities of this syndrome are unclear. Here we show that enhanced photosensitivity in mice was induced by treatment with a niacin antagonist as well as niacin-deficient diets, and that severe diarrhea with weight loss was induced by treatment with the niacin ntagonist, which suggest that this is a model of pellagra. Intriguingly, the niacin antagonist induced elevated expression of COX-2 and PGE syntheses (Ptges) mRNAs. The niacin antagonist treatment-induced photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. In line with the above findings in mice, analysis of skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Taken together, these findings indicate that niacin deficiency results in the development of photosensitivity in pellagra mediated by signaling through EP4 in response to increased PGE production.