外用钙调磷酸酶抑制剂（TCI）包括他克莫司软膏和吡美莫司霜是治疗特应性皮炎的热点药物，迄今TCI对皮肤朗格汉斯细胞（LC）的作用仍知之甚少。我们的预实验结果提示TCI能对抗长期低剂量UVB辐射引起的表皮LC减少；吡美莫司能通过抑制表皮LC迁移而逆转高剂量UVB辐射引起的表皮LC减少。IL-18、IL-1β、TNF-α、α-6整合素升高，E-钙黏附素降低均能促进LC迁移入真皮。有报道他克莫司能通过调节NF-κB抑制UVB辐射后角质形成细胞分泌TNF-α。为此，我们提出假说：他克莫司可能通过抑制UVB辐射后TNF-α的分泌进而抑制表皮LC迁移入真皮。为验证这一假说，我们将采用免疫组化、逆转录PCR、Western blot、流式细胞术等手段，从分子、细胞、组织等多方面探讨他克莫司抑制UVB辐射后LC迁移的具体机制。本研究将从他克莫司抑制表皮LC迁移这个新视点为TCI是否增加光致癌性提供新的证据

Topical calcineurin inhibitors (TCI), including tacrolimus ointment and pimecrolimus cream, are widely used in the treatment of atopic dermatitis. So far we still know little about the effects of TCI on epidermal Langerhans cell (LC). The results of our preliminary experiments suggested that TCI protected against long-term suberythemal UVB irradiation-induced epidermal LC reduction, and topical pimecrolimus could reverse high-dose UVB-induced LC reduction by inhibiting LC migration. The increase in the level of IL-18、IL-1β、TNF-α or integrin α6, and the decrease in the level of E-cadherin could promote LC migration from epidermis to dermis. It has been reported that tacrolimus dose-dependently downregulated the secretion of TNF-α from UVB-irradiated keratinocytes via regulation of NF-κB. Herein, we propose a hypothesis that TCI could inhibit UVB-induced LC migration by downregulating the secretion of TNF-α. To verify this hypothesis, we will use immunohistochemistry, reverse transcription-PCR, Western blot, flow cytometry and other means to investigate the specific mechanism of inhibition effects of tacrolimus on UVB-induced epidermal LC migration from molecules, cells, tissues and other aspects. This study would provide new evidence for safety study of TCI (increasing photocarcinogenesis?) from the new viewpoint of inhibition effects of TCI on epidermal LC migration.