Conditional ablation of Langerhans cells exacerbates autoimmune corneal inflammation (P5134)

Abstract

Abstract Ocular surface inflammation is common and sometimes severe in autoimmune diseases. Little is known about the role of cornea-resident dendritic cells, including Langerhans cells (LC), in ocular surface autoimmunity. Here, we analyzed corneal LC in autoimmune-prone MRL mice. LC (CD11c+ CD207+) were more abundant and activated (CD86+ CD40+) in the corneal epithelium of MRL mice than of B6 mice. However, LC were ~5-fold lower in the corneal stroma of MRL mice than of B6 mice. LC in cervical lymph nodes were also lower in MRL mice than in B6 mice. Ongoing studies will examine whether the increase of activated LC in corneal epithelium, but their reduction in corneal stroma and eye-draining lymph nodes in autoimmune mice is due to a defect in the migration of LC from the cornea to eye-draining lymph nodes. Since LC are believed to carry antigens from tissues to their respective draining lymph nodes to maintain tolerance in a tissue-specific manner, the reduced LC in eye-draining lymph nodes may lead to the breakdown of tolerance to eye antigens. To directly test the role of LC in ocular autoimmunity, we introgressed the Lang-eGFP.DTR knockin mutation from the stock B6 mice that express diphtheria toxin receptor (DTR) driven by Langerin promoter (Malissen, 2005) onto the MRL background. Diphtheria toxin injections depleted LC in Lang-eGFP.DTR MRL mice and accelerated corneal inflammation. Taken together, these data suggest a protective role of LC in corneal inflammation.