Background/Purpose: Patients with lupus and other systemic autoimmune diseases develop ocular surface inflammation that is sometimes severe and debilitating. Pathogenesis of autoimmune keratitis remains unclear. Cornea harbors local resident dendritic cells, including Langerhans cells (LC). LCs carry antigens from tissues to their respective draining lymph nodes to maintain local, organ-specific immune tolerance. Here, we investigated the role of Langerhans cells (LC) in ocular surface autoimmunity using animal models of lupus, MRL (MRL-lpr and MRL-Fas+/+).

Methods: We visualized LC in corneal epithelium and stroma by staining for CD11c and CD207. 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 (Lang) promoter onto the MRL background, and injected diphtheria toxin to deplete LCs in Lang-eGFP.DTR MRL mice.

Results: We found the increased numbers and more activated LCs (CD11c+CD207+; CD86+CD40+) in the corneal epithelium of MRL mice than of B6 mice. However, LCs were ~5-fold lower in the corneal stroma of MRL mice than of B6 mice. LCs were also lower in the eye-draining lymph nodes in MRL mice than in B6 mice. Repeated diphtheria toxin injections every 7-10 days in Lang-eGFP.DTR MRL mice completely depleted LC. LC-depleted MRL mice had significantly accelerated and severe corneal inflammation. LC-depleted mice had increased proliferation and activation of CD8+, but not CD4+, T-cells in eye-draining lymph nodes compared to LC-intact mice; such effect was not seen in spleen CD8+ T cells. Also, LC-ablated MRL, but not B6 mice, exhibited reduced CD62L on eye-draining lymph node T cells.

Conclusion: These results reveal a protective role of LCs in corneal inflammation. Accumulation of activated LC in corneal epithelium, but their reduction in corneal stroma and eye-draining lymph nodes, may suggest a possible impairment in the migration of LCs from the cornea to eye-draining lymph nodes in lupus-prone mice. The reduced LCs in the eye-draining lymph nodes may lead to the breakdown of T cell tolerance to eye antigens.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/role-of-corneal-langerhans-dendritic-cells-in-lupus-keratitis/