Study On The Potential Roles Of Langerin In The Epicutaneous Sensitization Of Atopic Dermatitis

Objective:Using Langerin knockout mice and C57BL/6 wild-type mice to establish AD mouse models induced by MC903 and ovalbumin(OVA),and exploring the effect and mechanism of Langerin on the skin and systemic inflammation of AD.Methods:1.Establishment of AD mouse model:Wild type female C57BL/6 mice were randomly divided into MC903,MC903+OVA group,and control group.AD model preparation was evaluated by examining skin lesions,ear swelling,skin histopathology(HE staining)and serum IgE,IgGl and IgG2a levels.2.Study on the immunomodulatory effect of Langerin on AD mouse model(1)Exploring whether Langerin was involved in the epicutaneous sensitization of MC903-induced AD mouse model:Langerin knockout and C57BL/6 wild-type mice were randomly divided into MC903 treated group and control group.The method of model preparation was the same as before.After the modeling,the degree of ear swelling,HE staining of ear lesions,total IgE level in serum,lymphocytes ratio of draining lymph nodes and expression of cytokines in skin lesions were compared.(2)Exploring whether Langerin was involved in the epicutaneous sensitization of OVA-induced AD mouse model:Langerin knockout and C57BL/6 wild-type mice were randomly divided into 2 AD model groups(OVA+MC903 and MC903)and 2 control groups(75%ethanol).With the continuous treatment for 12 days,the above indexes were detected thereafter.Results:1.Compared with the control groups,the skin of mice in the model groups showed significant tumidness and thickness,with keratosis and lymphocyte-dominated inflammatory cells infiltration in the superficial layer of the dermis,the difference was statistically significant(P<0.05).Total serum IgE and IgGl were significantly increased in the model groups.2.Study on the immunomodulatory effect of Langerin on AD mouse model(1)Langerin is not involved in the cutaneous inflammation of MC903-induced AD mouse model.In MC903 groups,the degree of skin tumidness and thickness,lymphocyte-dominated inflammatory cells infiltration,and the levels of serum IgE and TSLP expression were significantly higher than those of the control groups,the differences were statistically significant But there was no significant difference between WT and Langerin-KO groups.(2)Langerin is involved in the epicutaneous sensitization of OVA-induced AD mouse model.We established the model of MC903+OVA.The results showed that compared with wild-type mice,the skin tumidness and thickness,dermal inflammatory cells infiltration were much more obvious in the model groups than that of control groups(P<0.05);the number of CD11c+ dendritic cells,CD19+B cells in local lymph nodes were significantly increased in Langerin knockout mice;the number of CD4+CD25+CD127-Treg cells were decreased significantly;The total IgE level of Langerin knockout mice was significantly higher than that of wild-type mice;The mRNA expressions levels of TSLP,IL-4,IL-13,IL-17A and IL-22 in Langerin knockout mice were higher than those in wild-type mice(P<0.05).While,in the control groups,no significant difference was found between the Langerin knockout mice and the wild-type mice.Conclusion:Langerin might take part in the negative regulation of LCs in the epicutaneous sensitization of OVA-induced AD mouse models.