371 The OX40/OX40L axis plays a key role in treg dysfunction in atopic dermatitis

Recent clinical trials targeting the OX40-OX40L axis in atopic dermatitis/AD (AMG451, KHK4083, and KY1005) suggest potential for long-term disease modification. While inflammatory models that upregulate effector T cell survival inhibit Foxp3+ Tregs, mechanism of action remains unelucidated. We assessed OX40 OX40L expressing cells skin blood AD patients, identifying how they regulate effectors Tregs. evaluated lesional samples (n=14) controls using immunohistochemistry/IHC cultured human keratinocytes presence AD-related cytokines (IFN-γ, IL4, IL13, IL17, IL22) to measure TSLP expression. peripheral mononuclear cells/PBMCs from patients (n=28) (n=13) by flow cytometry. performed RNAseq analysis on CD4+ Tcells (CD4+CD127+CD25–) Tregs (CD4+CD25+CD127low) with IL2 or stimulated anti-CD3/28 absence (n=9) (n=10). IHC showed increased OX40+ OX40L+ cells, (P<0.001). Keratinocytes IL-13 significantly upregulated Flow cytometry characterized cutaneous lymphocyte antigen/CLA + homing CLA+ as a significant percent population (P<0.0001). correlated severity/SCORAD (R2=0.311, P<0.05). revealed OX40/OX40L interaction maintains Th2 functionality circulating but reduces regulatory capacity seen downregulation key markers IL10, IL4R, GZMH (P<0.05). The results indicate express interact skin, inhibits Treg’s ability ameliorate inflammation, Treg dysfunction correlates severity.