Kato Atsuhiko, Fujii Etsuko, Watanabe Takeshi, Takashima Yoshiaki, Matsushita Hiroaki, Furuhashi Takuya, Morita Akimichi
Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan.
Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan.
J Dermatol Sci. 2014 Jun;74(3):229-35. doi: 10.1016/j.jdermsci.2014.02.009. Epub 2014 Mar 12.
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.
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.
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).
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.
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.
为了解白细胞介素-31(IL-31)信号阻断疗法在特应性皮炎(AD)瘙痒中的临床环节,直接检测病变组织中的靶蛋白将提供关键信息。目前缺乏关于AD皮肤中IL-31细胞来源的直接证据,且AD中IL-31受体A(IL-31RA)表达的数据并不一致。此外,关于人类背根神经节(DRG)中IL-31RA蛋白表达尚无可用信息,而DRG介导瘙痒感觉且长期以来一直被怀疑是该蛋白的来源。
我们试图获取关于表达IL-31和IL-31RA蛋白的细胞在AD皮肤样本和人类DRG中的分布及其特征的直接证据。
采用免疫组织化学方法检测AD皮肤中的IL-31,并对代表性切片进行IL-31与几种免疫标志物的双重染色。采用免疫组织化学方法对AD皮肤和正常人DRG中的IL-31RA进行染色,并对代表性的AD皮肤进行IL-31RA与PGP9.5(一种神经标志物)的双重染色。
在重度AD样本中,IL-31阳性细胞表现为单核浸润细胞和共表达CD11b的细胞。至于IL-31RA,在AD真皮中的角质形成细胞和神经纤维以及正常DRG的神经元中检测到阳性反应。
在重度AD皮肤浸润细胞中检测到IL-31,在AD真皮神经纤维和正常DRG中检测到IL-31RA,表明IL-31信号可能是AD皮肤病变持续和加重的一个促成因素。