Objective: To explore the role of Langerin in mediating epicutaneous sensitization of atopic dermatitis (AD) in mouse model. Methods: Mice were topically treated with calcipotriol (MC903) plus ovalbumin (OVA) on the ears to establish AD mouse models, and mice were divided into wild-type control group, wild-type AD group, Langerin knockout control group, and Langerin knockout AD group. Changes of lesion were daily observed. Infiltration of inflammatory cells, mRNA expression of Tslp, Il4, Il13, Il17a, and Il22, levels of serum total IgE, OVA-specific IgE (sIgE), OVA sIgG1 and OVA sIgG2a, proportion of regulatory T (Treg) cells in cervical draining lymph nodes were evaluated at the end of model preparation. Results: Skin tumidness and thickness, dermal inflammatory cells infiltration, the mRNA expression levels of Tslp, Il4, Il13, Il17a and Il22 in wild-type AD groups were higher than those in wild-type control groups, with (1.80±0.66, 1.64±0.25, 1.71±0.54, 2.41±0.23, 2.49±0.32) and (0.53±0.45, 0.85±0.29, 0.73±0.50, 0.72±0.25, 0.56±0.29), respectively (all P<0.05). In addition, the levels of serum total IgE, OVA sIgE and OVA sIgG1 in wild-type AD groups were higher than those in wild-type control groups, with [(1 216.00±572.70) ng/ml, (597.00±538.30) ng/ml, 1.59±0.09] and [(24.22±35.04) ng/ml, (20.01±41.71) ng/ml, 1.16±0.03], respectively (all P<0.05). In Langerin knockout mice, compared to wild-type mice, skin erythema, skin tumidness, epidermal thickening, inflammatory cell infiltration were more obvious; the mRNA expression levels of Tslp, Il4, Il13, Il17a and Il22 were upregulated with (8.19±6.44, 2.53±0.69, 2.82±0.73, 3.94±1.32, 3.80±1.43) (all P<0.05); the levels of serum total IgE, OVA sIgE and OVA sIgG1 were significantly increased with (2 508.00±657.10) ng/ml, (1 808.00±470.70) ng/ml, (1.73±0.09) (all P<0.05); the number of CD4+CD25+CD127-Treg cells were decreased significantly with (13.25±0.96)% and (15.31±1.47)%, respectively (P<0.05). Conclusion: Langerin is involved in mediating epicutaneous sensitization of the AD mouse model and plays a negative immunoregulatory role.
目的： 探讨Langerin在介导特应性皮炎（AD）小鼠模型经皮致敏中的作用。 方法： 以Langerin基因敲除（Langerin-KO）小鼠及野生型小鼠为研究对象。对小鼠耳部进行卡泊三醇（MC903）和卵清蛋白（OVA）外涂制备AD模型，设置野生型对照组、野生型AD模型组、Langerin-KO对照组及Langerin-KO AD模型组4组小鼠。每日观察各组小鼠皮损变化情况。在造模结束后检测小鼠耳部皮损炎症细胞浸润情况，小鼠耳部皮损Tslp、Il4、Il13、Il17a和Il22 mRNA表达情况，血清总IgE、OVA特异性IgE（sIgE）、OVA sIgG1和OVA sIgG2a水平，以及小鼠颈部引流淋巴结Treg细胞数量变化。 结果： 与野生型对照组小鼠相比，野生型模型组小鼠耳部皮肤出现红斑、肿胀、鳞屑，表皮增厚、真皮炎症细胞浸润，耳部皮损中Tslp、Il4、Il13、Il17a和Il22的mRNA表达上调，分别为（1.80±0.66、1.64±0.25、1.71±0.54、2.41±0.23、2.49±0.32）和（0.53±0.45、0.85±0.29、0.73±0.50、0.72±0.25、0.56±0.29）（均P<0.05）。此外，与野生型对照组小鼠相比，野生型模型组小鼠血清总IgE、OVA sIgE和OVA sIgG1水平也升高，分别为［（1 216.00±572.70）ng/ml、（597.00±538.30）ng/ml、1.59±0.09］和［（24.22±35.04）ng/ml、（20.01±41.71）ng/ml、1.16±0.03］（均P<0.05）。在模型组中，Langerin-KO小鼠较野生型小鼠耳部皮肤红斑、肿胀、表皮增厚及真皮炎症细胞浸润更显著，耳部皮损中Tslp、Il4、Il13、Il17a和Il22的 mRNA表达进一步上调（8.19±6.44、2.53±0.69、2.82±0.73、3.94±1.32、3.80±1.43）（均P<0.05），血清总IgE、OVA sIgE、OVA sIgG1水平进一步升高［（2 508.00±657.10）ng/ml、（1 808.00±470.70 ng/ml）、（1.73±0.09）（均P<0.05）］，颈部引流淋巴结中CD4+CD25+CD127-Treg细胞比例下降，分别为（13.25±0.96）%和（15.31±1.47）%（P<0.05）。 结论： Langerin参与介导AD小鼠模型的经皮致敏并发挥负向免疫调控作用。.