Arsenic enhances Langerhans cell migration to draining lymph nodes via CCL21 and IFN-γproduction in a model of epicutaneous protein sensitization (89.19)

Abstract

Abstract Arsenic induces multiple Bowen's disease (As-BD), or cutaneous carcinoma in situ, that runs an indolent course. Immune responses are important modifiers for the development of As-BD. We have previously reported that Langerhans cells (LCs) were reduced in As-BD, but how arsenic alters LC migration and polarizes Th responses remains unknown. Using an epicutaneous protein sensitization model, Balb/c mice were patch-sensitized with OVA and received feeding of 300 ppm arsenic or PBS for 200ul for 5 days. Defined as CD207+MHCII+ cells, the number of LCs was significantly decreased in patched epidermis, but increased in draining lymph nodes, with no changes in dermis and spleens 96 hours after OVA sensitization in arsenic-treated mice. There was a parallel increase of CCL21 in lymph nodes from arsenic-treated mice, and enhanced cellular proliferation and IFN-γ secretion in vitro were also noted in lymph node cells from arsenic-treated mice. Notably, in vivo administration of a neutralizing antibody against CCL21 abolished the increase of LCs in lymph nodes. These results suggest, therefore, that in this model, arsenic exposure enhanced LC migration to draining lymph nodes via CCL21 and interferon-γ production, and that chronic nature of As-BD might result from enhanced Th1 responses and LC migration.