EpCAM Expressed by Murine Epidermal Langerhans Cells Modulates Immunization to an Epicutaneously Applied Protein Antigen.
Langerhans cells (LCs) induce type 2 antibodies reactive with protein antigens that are applied to murine skin in the absence of adjuvant after extending their dendrites through tight junctions to acquire antigens and migrating to regional lymph nodes. In response to contact sensitizers, epithelial cell adhesion molecule (EpCAM) on LCs promotes LC dendrite mobility and LC migration. In epithelial cells, EpCAM regulates expression and distribution of selected tight junctions-associated claudins. To determine if EpCAM regulates claudins in LC and immune responses to externally applied proteins, we studied conditional knockout mice with EpCAM-deficient LCs. Although LC claudin-1 levels were dramatically reduced in the absence of EpCAM, conditional knockout mice with EpCAM-deficient LCs and control LC dendrites docked with epidermal tight junctions with equal efficiencies and ingested surface proteins. Topical immunization of conditional knockout mice with EpCAM-deficient LCs with ovalbumin led to increased induction of type 2 Ova-specific antibodies and enhanced proliferation of ovalbumin-reactive T cells associated with increased accumulation of LCs in lymph nodes. These results suggest that, in the absence of strong adjuvants, EpCAM-deficient LCs exhibit increased migration to regional lymph nodes. EpCAM appears to differentially regulate LC mobility/migration in the setting of limited inflammation as compared with the intense inflammation triggered by contact sensitizers.
Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Takeshi
T
Ouchi
Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Gaku
G
Nakato
Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: udeym@mail.nih.gov.
Mark C
MC
Udey
D000818:Animals; D000941:Antigens / Q000276:immunology*; D002465:Cell Movement; D062445:Claudin-1 / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D007114:Immunization; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D019108:Tight Junctions / Q000378:metabolism*
D000941:Antigens; D062445:Claudin-1; C568113:Cldn1 protein, mouse; D000071858:Epithelial Cell Adhesion Molecule