Xiao Ting, Fujita Hideki, Saeki Hidehisa, Mitsui Hiroshi, Sugaya Makoto, Tada Yayoi, Kakinuma Takashi, Torii Hideshi, Nakamura Koichiro, Asahina Akihiko, Tamaki Kunihiko
Department of Dermatology, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan.
Cytokine. 2003;23(4-5):126-32. doi: 10.1016/s1043-4666(03)00221-7.
Thymus and activation-regulated chemokine (TARC/CCL17) is a Th2-type chemokine and its receptor CC chemokine receptor 4 (CCR4) is preferentially expressed on Th2 cells. Langerhans cells (LC) are immature dendritic cells (DC) in the epidermis of the skin and play vital roles in immune response. In this study, we investigated TARC expression by murine freshly isolated LC and 48 h cultured (mature) LC, and the regulation of TARC production in cultured LC by various cytokines. Murine LC was prepared using a panning method from BALB/c mice. RT-PCR was performed using fresh and cultured LC to evaluate TARC mRNA levels. ELISA was carried out using supernatant of cultured LC to calculate secreted TARC protein levels. TARC mRNA was strongly upregulated during maturation of murine LC. TARC production by murine LC was upregulated by TNF-alpha and IL-4 and downregulated by IFN-gamma, dose-dependently. Th1 and Th2 cytokines reciprocally regulate the production of Th2-type chemokine TARC by murine LC. Th2 cytokine microenvironments in skin may increase TARC production by mature LC, providing attraction of Th2 cells in skin. This may be an amplification circuit in Th2-dominant inflammatory skin disease like atopic dermatitis.
胸腺与激活调节趋化因子（TARC/CCL17）是一种Th2型趋化因子，其受体CC趋化因子受体4（CCR4）在Th2细胞上优先表达。朗格汉斯细胞（LC）是皮肤表皮中的未成熟树突状细胞（DC），在免疫反应中起重要作用。在本研究中，我们调查了小鼠新鲜分离的LC和培养48小时（成熟）的LC中TARC的表达情况，以及各种细胞因子对培养的LC中TARC产生的调节作用。使用淘选法从BALB/c小鼠制备小鼠LC。使用新鲜和培养的LC进行RT-PCR以评估TARC mRNA水平。使用培养的LC的上清液进行ELISA以计算分泌的TARC蛋白水平。在小鼠LC成熟过程中，TARC mRNA强烈上调。小鼠LC产生的TARC被TNF-α和IL-4上调，并被IFN-γ剂量依赖性下调。Th1和Th2细胞因子相互调节小鼠LC产生Th2型趋化因子TARC。皮肤中的Th2细胞因子微环境可能会增加成熟LC产生TARC，从而吸引皮肤中的Th2细胞。这可能是特应性皮炎等Th2主导的炎症性皮肤病中的一个放大回路。
