505 Therapeutic activity of an anti-IL36R blocking antibody in inhibiting atopic dermatitis-like skin inflammation in mice

Staphylococcus aureus epicutaneous exposure to mouse skin was previously found to induce atopic dermatitis (AD)-like inflammation that was dependent upon IL-36 receptor (IL-36R) activity. However, whether systemic treatment with an anti-IL-36R blocking monoclonal antibody (mAb) could have a therapeutic effect by diminishing IL-36-dependent S. aureus-induced skin inflammation is unclear. Herein, we evaluated the efficacy of an IL-36R blocking mAb in inhibiting AD-like inflammation induced by S. aureus epicutaneous exposure to mouse skin. S. aureus epicutaneous exposure was performed by applying a S. aureus (1 x 108 CFU) soaked gauze pad for 7 days on dorsal skin while the mice were treated with systemic administration (intraperitoneal) of an anti-IL-36R blocking mAb or isotype control mAb on days -1, 2 and 5. The anti-IL-36R blocking mAb treatment resulted in significantly decreased AD-like skin inflammation as measured by disease score (edema, erythema, necrosis and scaling) by a blinded evaluator, epidermal thickness quantified from histologic sections, and decreased neutrophil recruitment but not total or IL-17-producing T cell (CD3+, γδ, CD4+ and CD8+ T cell subsets) recruitment to the skin as measured by flow cytometry compared with isotype control-treated mice. Taken together, anti-IL-36R blocking mAb treatment inhibited AD-like skin inflammation induced by S. aureus epicutaneous exposure in a mechanism associated with decreased neutrophil but not T cell recruitment to the affected skin.