Related Experiment Video
Updated: Mar 22, 2026
Murine Model of Epicutaneously-Induced Immunomodulation
Published on: June 24, 2025
EpCAM Expressed by Murine Epidermal Langerhans Cells Modulates Immunization to an Epicutaneously Applied Protein
Takeshi Ouchi1, Gaku Nakato1, Mark C Udey1
1Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Insights
Epithelial cell adhesion molecule (EpCAM) deficiency in Langerhans cells (LCs) enhances their migration to lymph nodes, boosting type 2 antibody responses to protein antigens without adjuvants.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Langerhans cells (LCs) are critical for skin immunity, acquiring antigens and migrating to lymph nodes.
- Epithelial cell adhesion molecule (EpCAM) influences LC migration in response to contact sensitizers.
- EpCAM's role in regulating tight junctions and LC function in the absence of strong adjuvants is unclear.
Purpose of the Study:
- To investigate the function of EpCAM in LCs regarding antigen uptake and immune responses.
- To determine if EpCAM regulates claudins in LCs and their migration to lymph nodes.
- To assess the impact of EpCAM deficiency in LCs on type 2 immune responses to topical protein antigens.
Main Methods:
- Utilized conditional knockout mice with EpCAM-deficient LCs.
- Examined LC dendrite interactions with epidermal tight junctions.
- Assessed antigen uptake and LC migration to lymph nodes following topical ovalbumin immunization.
Main Results:
- EpCAM deficiency in LCs reduced claudin-1 levels but did not impair tight junction docking or antigen ingestion.
- Conditional knockout mice with EpCAM-deficient LCs showed increased LC accumulation in lymph nodes.
- Topical ovalbumin immunization induced higher levels of type 2 Ova-specific antibodies and enhanced T cell proliferation in these mice.
Conclusions:
- EpCAM deficiency in LCs enhances their migration to lymph nodes, particularly in low-inflammation settings.
- EpCAM plays a differential role in LC migration depending on the inflammatory context.
- Targeting EpCAM in LCs may offer a strategy to augment immune responses to skin-applied antigens without adjuvants.
Abstract:
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.
