Kikuchi Sota, Yanaba Koichi, Nobeyama Yoshimasa, Yabe Shigeharu, Kiso Masahiro, Saeki Hidehisa, Tada Yayoi, Nakagawa Hidemi, Okochi Hitoshi
Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Ann Dermatol. 2017 Aug;29(4):391-399. doi: 10.5021/ad.2017.29.4.391. Epub 2017 Jun 21.
Allergic contact dermatitis (ACD), which is accelerated by interferon (IFN)-γ and suppressed by interleukin (IL)-10 as regulators, is generally self-limited after removal of the contact allergen. Adipose tissue-derived multipotent mesenchymal stem cells (ASCs) potentially exert immunomodulatory effects. Considering that subcutaneous adipose tissue is located close to the site of ACD and includes mesenchymal stem cells (MSCs), the MSCs in adipose tissue could contribute to the self-limiting course of ACD.
The aims of the present study were to elucidate the effects of MSCs in adipose tissue on ACD and to examine any cytokine-mediated mechanisms involved.
Ear thickness in a C57BL/6 mouse model of ACD using contact hypersensitivity (CHS) elicited by 2,4,6-trinitro-1-chlorobenzene was evaluated as a marker of inflammation level. Five and nine mice were injected with ASCs and phosphate-buffered saline (PBS), respectively. After ASC or PBS injection, real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were performed.
Histology showed that CHS was self-limited and ear thickness was suppressed by ASCs in a dose-dependent manner. IFN-γ expression in the elicited skin site and regional lymph nodes was significantly lower in ASC-treated mice than in control mice. IL-10 expression did not differ between treated and control mice. The suppressive effects of ASCs on CHS response did not differ between IL-10 knock-out C57BL/6 mice and wild-type mice.
The present findings suggest that MSCs in adipose tissue may contribute to the self-limiting course of ACD through decreased expression of IFN-γ, but not through increased expression of IL-10.
过敏性接触性皮炎（ACD）通常在去除接触性变应原后会自我限制，它可被干扰素（IFN）-γ加速，并被白细胞介素（IL）-10作为调节因子所抑制。脂肪组织来源的多能间充质干细胞（ASC）可能发挥免疫调节作用。鉴于皮下脂肪组织位于ACD部位附近且包含间充质干细胞（MSC），脂肪组织中的MSC可能有助于ACD的自我限制过程。
本研究旨在阐明脂肪组织中的MSC对ACD的影响，并研究其中涉及的任何细胞因子介导的机制。
在使用2,4,6-三硝基-1-氯苯引发接触性超敏反应（CHS）的C57BL/6小鼠ACD模型中，将耳部厚度作为炎症水平的标志物进行评估。分别向5只和9只小鼠注射ASC和磷酸盐缓冲盐水（PBS）。在注射ASC或PBS后，进行实时逆转录-聚合酶链反应和酶联免疫吸附测定。
组织学显示CHS是自我限制的，ASC以剂量依赖性方式抑制耳部厚度。在ASC处理的小鼠中，引发的皮肤部位和局部淋巴结中的IFN-γ表达明显低于对照小鼠。处理组和对照组小鼠之间的IL-10表达没有差异。在IL-10基因敲除的C57BL/6小鼠和野生型小鼠之间，ASC对CHS反应的抑制作用没有差异。
本研究结果表明，脂肪组织中的MSC可能通过降低IFN-γ的表达，而不是通过增加IL-10的表达，来促进ACD的自我限制过程。
