Dendritic Cell (DC)-Specific Targeting Reveals Stat3 as a Negative Regulator of DC Function

摘要: Dendritic cells (DCs) must achieve a critical balance between activation and tolerance, process influenced by cytokines growth factors. IL-10, which transduces signals through Stat3, has emerged as one important negative regulator of DC activation. To directly examine the role Stat3 plays in regulating activity, gene was targeted for deletion with CD11c-cre transgene. CKO mice developed cervical lymphadenopathy well mild ileocolitis that persisted throughout life associated impaired weight gain. Consistent this, Stat3-deficient DCs demonstrated enhanced immune including increased cytokine production, Ag-dependent T-cell resistance to IL-10-mediated suppression. These results reveal cell-intrinsic regulatory link perturbed homeostasis chronic mucosal inflammation.