Vestergaard C, Yoneyama H, Murai M, Nakamura K, Tamaki K, Terashima Y, Imai T, Yoshie O, Irimura T, Mizutani H, Matsushima K
Department of Molecular Preventive Medicine, University of Tokyo, Tokyo 113-0033, Japan.
J Clin Invest. 1999 Oct;104(8):1097-105. doi: 10.1172/JCI7613.
We have examined the expression of chemokines and their receptors in the atopic dermatitis-like (AD-like) lesions of NC/Nga mice. Such lesions develop when the mice are kept in conventional conditions, but not when they are kept isolated from specific pathogens. The thymus- and activation-regulated chemokine TARC is unexpectedly highly expressed in the basal epidermis of 14-week-old mice with lesions, whereas it is not expressed in the skin without lesions. Production of TARC by keratinocytes was confirmed by culturing murine keratinocytic cell line cells (PAM212) with TNF-alpha, IFN-gamma, or IL-1beta. Expression of another Th2 chemokine, macrophage-derived chemokine (MDC), was observed in the skin from mice kept in both conventional and pathogen-free conditions, but expression of MDC was increased severalfold in the skin with lesions. The cellular origin of MDC was identified to be dermal dendritic cells. Infiltration of the skin by IL-4-producing T cells and mast cells, and the increase of CCR4 mRNA in the skin, coincided with the development of AD lesions. These observations indicate that TARC and MDC actively participate in the pathogenesis of AD-like lesions in NC/Nga mice and that these Th2 chemokines could be novel targets for intervention therapy of AD in humans.
我们检测了趋化因子及其受体在NC/Nga小鼠特应性皮炎样（AD样）皮损中的表达。当小鼠饲养在常规条件下时会出现此类皮损，但饲养在与特定病原体隔离的环境中则不会出现。胸腺和活化调节趋化因子TARC在14周龄有皮损的小鼠的基底表皮中意外地高表达，而在无皮损的皮肤中不表达。通过用肿瘤坏死因子-α、干扰素-γ或白细胞介素-1β培养小鼠角质形成细胞系细胞（PAM212），证实了角质形成细胞可产生TARC。在饲养于常规条件和无病原体条件下的小鼠皮肤中均观察到另一种Th2趋化因子——巨噬细胞衍生趋化因子（MDC）的表达，但在有皮损的皮肤中MDC的表达增加了数倍。MDC的细胞来源被确定为真皮树突状细胞。产生白细胞介素-4的T细胞和肥大细胞浸润皮肤，以及皮肤中CCR4 mRNA的增加，与AD皮损的发展一致。这些观察结果表明，TARC和MDC积极参与NC/Nga小鼠AD样皮损的发病机制，并且这些Th2趋化因子可能是人类AD干预治疗的新靶点。
