Langerhans Cells Prevent Autoimmunity via Expansion of Keratinocyte Antigen-Specific Regulatory T Cells

摘要: Langerhans cells (LCs) are antigen-presenting in the epidermis whose roles antigen-specific immune regulation remain incompletely understood. Desmoglein 3 (Dsg3) is a keratinocyte cell-cell adhesion molecule critical for epidermal integrity and an autoantigen autoimmune blistering disease pemphigus. Although antibody-mediated mechanisms pemphigus extensively characterized, T cell aspect of this still remains poorly Herein, we utilized mouse model CD4+ cell-mediated autoimmunity against Dsg3 to show that acquisition subsequent presentation by LCs depended on C-type lectin langerin. The lack led enhanced with impaired Dsg3-specific regulatory expansion. expressed IL-2 receptor complex disruption signaling attenuated LC-mediated expansion vitro, demonstrating direct shapes LC function. These data establish mediate peripheral tolerance point langerin pathways as attractive targets achieving tolerogenic responses particularly diseases such