201 Decreased efficacy of regulatory T cells in the absence of HCA2 is due to overexpression of IL-6

The suppressive activity of regulatory T cells (Treg) in the absence G-protein coupled receptor 109a (HCA2, Puma) is significantly reduced as demonstrated contact hypersensitivity model. Here we asked whether same phenomenon can be observed other skin inflammatory models. To address this issue, used psoriasis like imiquimod (IMQ)-induced inflammation model mice. Application IMQ on HCA2- knock out (KO) or wild type (WT) animals resulted psoriasiform (skin thickening, erythema, scales). response was stronger HCA2-KO animals. Histopathological analysis revealed that induced acanthosis, hyperkeratosis and an infiltrate which were more pronounced HCA2-KO. applied for splenomegaly by IMQ. Flow cytometry Foxp3+ obtained from lymph nodes spleens IMQ-treated upregulated expression IL-6 comparison to WT study immunosuppressive Treg responsible enhancement inflammation, mice injected into In contrast Treg, did not suppress effect IMQ, but even enhanced disease pattern. Since suppresses development next studied proinflammatory effect. isolated KO treated with a monoclonal anti-IL-6- antibody. mitigated recipients anti-IL6-treated compared untreated HCA-KO donors. epidermal effects anti-IL-6-treated donors, suggesting overexpression might functional failure Treg.