Mechanisms of Itch in Stasis Dermatitis: Significant Role of IL-31 from Macrophages
Mechanisms of Itch in Stasis Dermatitis: Significant Role of IL-31 from Macrophages
复制标题
DOI：
10.1016/j.jid.2019.09.012
复制
发表时间：
2020-04-01
影响因子：
6.5
通讯作者：
Yosipovitch, Gil
中科院分区：
文献类型：
--
作者：
Hashimoto, Takashi;Kursewicz, Christina Dorothy;Yosipovitch, Gil
瘀积性皮炎(SD)是老年人群的常见病，瘙痒是其常见症状之一。然而，由于对其病理生理机制知之甚少，目前治疗SD相关性瘙痒的方法很少。因此，我们试图通过一项以IL-31为重点的患者皮损的免疫荧光研究来调查SD患者瘙痒的介质。使用小鼠腹膜巨噬细胞的体外刺激研究也被用来阐明IL-31产生的病理机制。SD皮损真皮浸润性IL-31(+)细胞较健康对照组增多，且以CD68(+)巨噬细胞为主。SD患者瘙痒的发生与CD68(+)/IL-31(+)巨噬细胞和CD68(+)/CD163(+)M2巨噬细胞数量显著相关。CD68(+)/IL-31(+)巨噬细胞数与真皮C-C趋化因子受体4(+)T辅助细胞数、IL-17(+)细胞数、嗜碱性粒细胞、P物质(+)细胞数、真皮中Periostin和含铁血黄素沉积数呈正相关。此外，当P物质、Periostin和红细胞裂解物(代表含铁血黄素)的组合刺激时，小鼠腹膜巨噬细胞表达M2标记精氨酸酶-1并产生IL-31。巨噬细胞产生的IL-31可能在SD的瘙痒发病中起一定作用。
Stasis dermatitis (SD) is a common disease in the elderly population, with pruritus being one of the troublesome symptoms. However, there are few therapeutic modalities available for SD-associated itch because little is known about its pathophysiological mechanism. Therefore, we sought to investigate the mediators of itch in SD using an immunofluorescence study on patient lesions focusing on IL-31. Ex vivo stimulation studies using murine peritoneal macrophages were also used to elucidate the pathological mechanisms of the generation of IL-31. In SD lesions, dermal infiltrating IL-31(+) cells were increased in number compared with the healthy controls, and the majority of IL-31(+) cells were CD68(+) macrophages. The presence of itch in SD was significantly associated with the amount of CD68(+)/IL-31(+) macrophages and CD68(+)/CD163(+) M2 macrophages. The number of CD68(+)/IL-31(+) macrophages was correlated with the number of dermal C-C chemokine receptor type 4(+) T helper type 2 cells, IL-17(+) cells, basophils, substance P(+) cells, and dermal deposition of periostin and hemosiderin. Furthermore, murine peritoneal macrophages expressed an M2 marker arginase-1 and generated IL-31 when stimulated with a combination of substance P, periostin, and red blood cell lysate (representing hemosiderin). IL-31 from macrophages may play a role in itch in SD.