Atsuhiko Kato1, Etsuko Fujii2, Takeshi Watanabe3, Yoshiaki Takashima2, Hiroaki Matsushita2, Takuya Furuhashi4, Akimichi Morita4. 1. Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan. Electronic address: katoath@chugai-pharm.co.jp. 2. Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan. 3. Chugai Research Institute for Medical Science Inc., 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan. 4. Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya-shi, Aichi 467-8602, Japan.
Abstract
BACKGROUND: To understand the clinical segments of IL-31 signaling blockade therapy in pruritus of atopic dermatitis (AD), direct detection of the target proteins in the diseased tissues will provide crucial information. There is a lack of direct evidence concerning the cellular origin of IL-31 in AD skins, and data on the expression of IL-31RA in AD are inconsistent. Also, there is no available information regarding IL-31RA protein expression in human dorsal root ganglia (DRG), which mediates the sensation of itch and is the long-suspected source of the protein. OBJECTIVE: We sought to obtain direct evidence concerning the distribution of IL-31- and IL-31RA-protein expressing cells and their characteristics in AD skin samples and in human DRG. METHODS: IL-31 was detected immunohistochemically in AD skins, and representative sections were double stained with IL-31 and several immune-markers. IL-31RA was stained immunohistochemically in AD skins and normal human DRG, and representative AD skins were double stained with IL-31RA and PGP9.5 (a nerve marker). RESULTS: IL-31-positive cells were observed as mononuclear infiltrating cells and as CD11b co-expressing cells in severe AD samples. As for IL-31RA, positive reactions were detected in keratinocytes and nerve fibers in the dermis of AD and in the neurons of normal DRG. CONCLUSION: The detection of IL-31 in infiltrating cells of severe AD skin and of IL-31RA in nerve fibers of AD dermis and normal DRG indicates IL-31 signaling may be a contributing factor in the persistence and exacerbation of AD skin lesions.
BACKGROUND: To understand the clinical segments of IL-31 signaling blockade therapy in pruritus of atopic dermatitis (AD), direct detection of the target proteins in the diseased tissues will provide crucial information. There is a lack of direct evidence concerning the cellular origin of IL-31 in AD skins, and data on the expression of IL-31RA in AD are inconsistent. Also, there is no available information regarding IL-31RA protein expression in human dorsal root ganglia (DRG), which mediates the sensation of itch and is the long-suspected source of the protein. OBJECTIVE: We sought to obtain direct evidence concerning the distribution of IL-31- and IL-31RA-protein expressing cells and their characteristics in AD skin samples and in human DRG. METHODS:IL-31 was detected immunohistochemically in AD skins, and representative sections were double stained with IL-31 and several immune-markers. IL-31RA was stained immunohistochemically in AD skins and normal human DRG, and representative AD skins were double stained with IL-31RA and PGP9.5 (a nerve marker). RESULTS:IL-31-positive cells were observed as mononuclear infiltrating cells and as CD11b co-expressing cells in severe AD samples. As for IL-31RA, positive reactions were detected in keratinocytes and nerve fibers in the dermis of AD and in the neurons of normal DRG. CONCLUSION: The detection of IL-31 in infiltrating cells of severe AD skin and of IL-31RA in nerve fibers of AD dermis and normal DRG indicates IL-31 signaling may be a contributing factor in the persistence and exacerbation of AD skin lesions.
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