Langerhans cells (LC) are potent antigen presenting cells localized in the epidermis. LC express high levels of the adhesion molecule E-Cadherin (E-cad) which has been suggested to be responsible for adhesion to keratinocytes and thus LC localization to the epidermis, supported by three lines of evidence: formation of adherens junctions between E-cad expressing LC like dendritic cells and keratinocytes, down regulation of E-cad during activation, maturation and emigration of LC, and requirement of TGF-β for E-cad expression in dendritic cells (DC) and lack of epidermal LC in TGF-β null mutants. Since most of this evidence is indirect, we here address the question whether E-cad expression in LC is required for their epidermal localization in vivo. For this we used mice with a selective deficiency for E-Cad in CD11c+ cells generated by Cre/LoxP mediated recombination. In E-cadfl/flCD11c Cre+ mice E-cad expression was absent in LC as shown by flow cytometry. Surprisingly, lack of E-cad in LC had little effect on epidermal localization of LC as demonstrated by almost normal LC numbers in epidermal sheets and whole mount skin in Cre+ mice as compared to Cre- littermates. No differences were observed with regard to activation status of LC, in vivo LC migration to regional lymph nodes and TNCB induced contact hypersensitivity. In contrast, in vitro significantly more LC could be isolated from the epidermis of Cre+ mice than that of Cre- controls, which may indicate that E-cad is involved but not essential for adhesion of LC to epidermal keratinocytes. In conclusion our findings reveal that despite the lack of E-cad LC are still largely present in the epidermis, suggesting that E-Cadherin is dispensable for localization of LC within the epidermal layers of the skin.

E-Cadherin is dispensable for epidermal localization of Langerhans cells