Transportation of sublingual antigens across sublingual ductal epithelial cells to the ductal antigen-presenting cells in mice

Background: Sublingual immunotherapy (SLIT) has proven to be safe and efficient for the treatment of type I allergies. However, the mechanisms underlying allergen transportation within the sublingual compartment, the localization of antigens, and the identities of the cells responsible for this immunization remain incompletely understood. Objective: In this study, we focused on the sublingual ductal system and analysed the localization and transportation of antigens after their sublingual application. Methods: In mice given adjuvant-free antigens sublingually, tissues were removed at 0, 0.5, 1, or 2 h after the application and subjected to immunohistochemistry. Cells isolated from the sublingual duct and mucosa were analysed by flow cytometry. Results: Substantial immunoreactivity to ovalbumin (OVA) was evident in sublingual ductal epithelial cells at 30 min and 1 h after sublingual administration of OVA, but it had disappeared at 2 h. The ductal epithelial cells incorporated not only OVA, but also particulate antigens such as latex or silica beads and microbes. MHC class II (MHCII)⁺ antigen-presenting cells (APCs) were located around the sublingual ductal system, and MHCII⁺ cells were co-localized with, and around, antigen-incorporated sublingual duct cells. CD11b⁺ CD11c^- cells were present among CD45⁺ MHCII⁺ cells at greater frequency in the sublingual duct than in the sublingual mucosa, and they were the main contributors to the incorporation of OVA in vitro. Conclusions and Clinical Relevance: This study reveals that sublingual antigens can be transported across sublingual ductal epithelial cells to the ductal APCs. If the system is the same in humans as in mice, the ductal APCs may prove to be important target cells for SLIT.