072 The anti-inflammatory cytokine IL-37 inhibits CD4+ T cell activation through the receptor IL-1R8 and supports regulatory T cells

IL-1 family member IL-37 inhibits both innate and adaptive immune responses. Previously, we have shown that intracellular expression in monocytes dendritic cells reduces inflammation induces tolerance. However, the role of extracellular on T cell activation remains unknown. Extracellularly, has been found to form a tripartite ligand-receptor complex containing IL-1R8 (SIGIRR/TIR8) IL-18Ra monocytes. We used human CD4 from healthy donors, transgenic mice expressing IL-37, deficient study activation. Treatment CD4+ with recombinant reduced TCR-mediated signaling activation, T-cell proliferation, pro-inflammatory cytokine production. Because was highly expressed regulatory (Treg) cells, compared effects conventional (Tconv) Treg using wild-type (WT) mice, IL-1R8-deficient mice. Recombinant directly inhibited canonical pathways through Tconv indicating direct anti-inflammatory suppressing cell-mediated immunity. On other hand, without affecting Treg-specific gene expression, suggesting endogenous helps retain high levels signatures even presence IL-37. IL-37’s inhibitory definition now includes