ZhiQiang Yin,1,* JiaLi Xu,2,* BingRong Zhou,1 Di Wu,1 Yang Xu,1 JiaAn Zhang,1 Dan Luo1 1Department of Dermatology, 2Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Guangzhou Road, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Background: Topical pimecrolimus has been shown to reverse epidermal CD1a+ Langerhans cell reduction induced by high-dose ultraviolet (UV)B irradiation, but the mechanism is still unclear. This study aimed to investigate the possible mechanism of the effect of pimecrolimus on high-dose UVB-irradiated epidermal Langerhans cells.Methods: Forty human foreskin tissues were divided into four groups: control; pimecrolimus-only; UVB-only; and UVB + pimecrolimus. All tissues were cultured, and each tissue was cut into four pieces, corresponding to four time points (0 hours, 18 hours, 24 hours, and 48 hours). We collected the tissues and culture medium at each time point. The percentage of CD1a+ cells in medium was detected by flow cytometry. The tissues were detected for messenger (m)RNA and protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and E-cadherin, by reverse-transcription polymerase chain reaction (PCR) and western blot.Results: At 18 hours, 24 hours, and 48 hours, the CD1a+ cells in the culture medium of the UVB-only group and the UVB + pimecrolimus group were significantly more than in the control group, while the CD1a+ cells of the UVB + pimecrolimus group was less than of the UVB-only group. For both the UVB-only group and UVB + pimecrolimus group, TNF-α expression (by both reverse-transcription PCR and western blot) of the tissues was clearly higher and E-cadherin expression was significantly lower compared with the control group, at 18 hours, 24 hours, and 48 hours. For the UVB + pimecrolimus group, TNF-α was clearly lower and E-cadherin was significantly higher compared with the UVB-only group.Conclusion: Topical pimecrolimus inhibited epidermal Langerhans cell migration induced by high-dose UVB irradiation, via regulation of TNF-α and E-cadherin. Keywords: pimecrolimus, UVB, Langerhans cell, TNF-α, E-cadherin