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Resolution is the active, programmed termination of tissue inflammation and the restoration of tissue homeostasis. Although this concept is mainly derived from observation made in mouse models of peracute peritonitis, it has been suggested that failing resolution is responsible for the emergence of chronic tissue inflammation. 12/15-lipoxygenase (12/15-LO) is a key enzyme for the biosynthesis of specialized proresolving lipid mediators (SPMs) and it is believed to be a major orchestrator of resolution. The role of 12/15-LO in the regulation of dermatitis, including pemphigoid diseases, which are characterized by production of autoantibodies targeting the structural proteins of the skin, is, however, unknown. We have therefore addressed the role of 12/15-LO in the antibody transfer bullous pemphigoid (BP)-like EBA mouse model, using the 12/15-LO deficient (Alox15−/−) mice. In this model, pemphigoid diseaselike dermatitis was pronouncedly aggravated and prolonged in Alox15−/− mice in comparison with wild-type mice. Moreover, elevated levels of docosahexaenoic acidderived SPMs, including 10, 17-DiHDHA, 17 (S)-HDHA, and 14 (S)-HDHA were found in lesional skin of wild-type mice, but not in the skin of Alox15−/− mice, indicating, that 12/15-LO counteracts skin inflammation and is involved in its resolution via the biosynthesis of SPMs. Herein, 12/15-LO expression was induced in skin infiltrating PMNs, suggesting that PMNs participate in both initiation and termination of skin inflammation in this model. Moreover, In line with a similar role of 12/15-LO in the human situation, we have found its upregulation in lesional skin of bullous …