EpCAM expressed by epidermal langerhans cells modulates immunization to an epicutaneously-applied protein antigen

Abstract

Langerhans cells (LC) are required for efficient formation of Type 2 (IgG1 and IgE) Ab in response to foreign proteins that are applied to skin without adjuvant. Immunization is mediated via LC that extend dendrites through tight junctions (TJ) to acquire topically applied Ag and subsequently migrate to regional lymph nodes (LN). EpCAM (CD326) is expressed at high levels by LC. We previously reported that EpCAM promotes LC dendrite mobility, as well as LC migration within epidermis and from epidermis to regional LN in response to contact sensitizers. We also demonstrated that, in intestinal epithelial cells, EpCAM regulates the levels of expression and distribution of selected claudins. We hypothesized that in the absence of EpCAM, acquisition of Ag by LC might be impaired and topical immunization to proteins might be reduced. To test this, we studied conditional KO mice with EpCAM-deficient LC (cKO mice). Control (WT) and cKO LC dendrites docked with and penetrated the epidermal TJ with equal efficiencies. LC from both strains internalized surface biotinylated self-proteins. Unexpectedly, topical immunization of cKO mice with ovalbumin (Ova) led to the accumulation of increased numbers of LC in regional LN. This was accompanied by enhanced proliferation of adoptively transferred Ova- reactive OT-II cells and enhanced formation of Ova-specific Ab in cKO mice. These results indicate that EpCAM regulates topical immunization to protein acting via LC, but immunization is potentiated by EpCAM deficiency rather than inhibited. We propose that EpCAM-dependent mechanisms that regulate LC migration may differ in the setting of limited inflammation associated with topical immunization with protein as compared with the intense inflammation triggered by strong contact sensitizers.