Cutaneous immune responses to niacin in photosensitivity

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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.