Katagiri Kazumoto, Arakawa Shoko, Hatano Yutaka, Fujiwara Sakuhei
Department of Dermatology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Oita 879-5593, Japan.
Arch Dermatol Res. 2008 Nov;300(10):583-93. doi: 10.1007/s00403-008-0865-y. Epub 2008 Jun 5.
Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that frequently begins at infancy and the majority of them develop asthma and/or allergic rhinitis later, in which food and inhaled allergens play an important role. There is a murine model for AD that is induced by repeated epicutaneous (e.c.) exposure with ovalbumin (OVA). This model shares many characteristic features with AD, including development of asthma as well as dermatitis. Recently, it is reported that ocular tolerance or tolerance induced by intravenous administration of in vitro generated tolerogenic antigen-presenting cells (tol-APC), which can bypasses ocular tolerance, inhibits the immune response in a murine asthma model. The present study was designed to investigate whether tolerance induced by tol-APC and ocular tolerance inhibits AD-like dermatitis induced by repeated e.c. sensitization with OVA. BALB/c mice were given a total of three 1 week e.c. exposures to OVA with 2-week intervals between exposures. After second exposure to OVA, mice received the tol-APC or received OVA in the anterior chamber (AC) of the eye (ocular tolerance). Both groups of mice received the tol-APC and mice that received OVA in the AC of the eye showed weakened cellular infiltration in the skin including eosinophils and mast cells, lower levels of antigen-specific IgE, lower levels of transcripts of IL-4, IL-5, IL-13 in the skin and less production of Th1 and Th2 cytokine by regional lymph node cells, compared with those of mice that received sham treatment and mice that received the tol-APC treated with unrelated antigen after second e.c. exposure to OVA. These results indicate that antigen-specific tolerance induced by the tol-APC and ocular tolerance can inhibit the dermatitis and its related systemic immune response in the murine AD model. These types of tolerance might lead to a new therapeutic approach to allergic skin disease.
特应性皮炎（AD）是一种慢性瘙痒性炎症性皮肤病，通常始于婴儿期，大多数患者随后会发展为哮喘和/或过敏性鼻炎，食物和吸入性过敏原在其中起重要作用。有一种AD的小鼠模型是通过反复经皮（e.c.）暴露于卵清蛋白（OVA）诱导产生的。该模型与AD具有许多共同特征，包括哮喘和皮炎的发展。最近，有报道称，眼部耐受或通过静脉注射体外产生的致耐受性抗原呈递细胞（tol-APC）诱导的耐受（可绕过眼部耐受）可抑制小鼠哮喘模型中的免疫反应。本研究旨在调查tol-APC诱导的耐受和眼部耐受是否能抑制由OVA反复经皮致敏诱导的类AD性皮炎。将BALB/c小鼠共进行三次经皮暴露于OVA，每次暴露1周，暴露间隔为2周。在第二次暴露于OVA后，小鼠接受tol-APC或在眼前房（AC）注射OVA（眼部耐受）。与接受假处理的小鼠以及在第二次经皮暴露于OVA后接受用无关抗原处理的tol-APC的小鼠相比，两组接受tol-APC的小鼠和在眼前房注射OVA的小鼠皮肤中的细胞浸润（包括嗜酸性粒细胞和肥大细胞）减弱，抗原特异性IgE水平降低，皮肤中IL-4、IL-5、IL-13的转录水平降低，区域淋巴结细胞产生的Th1和Th2细胞因子减少。这些结果表明，tol-APC诱导的抗原特异性耐受和眼部耐受可抑制小鼠AD模型中的皮炎及其相关的全身免疫反应。这些类型的耐受可能会导致一种治疗过敏性皮肤病的新方法。
