On/Off TLR Signaling Decides Proinflammatory or Tolerogenic Dendritic Cell Maturation upon CD1d-Mediated Interaction with Invariant NKT Cells

摘要: Invariant NKT (iNKT) cells play an effector/adjuvant function during antimicrobial and antitumoral immunity a regulatory role to induce immune tolerance prevent autoimmunity. iNKT that differentially modulate adaptive do not bear unique phenotype and/or specific cytokine secretion profile, thus opening questions on how single T cell subset can exert opposite immunological tasks. In this study, we show perform their dual roles through mechanism of action relying the cognate interaction with myeloid dendritic (DCs) leading effects depending presence other maturation stimuli simultaneously acting DCs. The contact murine purified immature autologous DCs directly triggers tolerogenic DCs, rendering them able differentiation autoimmune diabetes in vivo. Conversely, same simultaneous TLR4 stimulation, significantly enhances proinflammatory DC IL-12 secretion. different are mediated distinct mechanisms activation molecular pathways within DC: CD1d signaling ERK1/2 pathway for action, CD40-CD40L NF-κB adjuvant effect. Our data suggest decision undergo or results from integration signals received at time could have important therapeutic implications exploiting adjuvant/regulatory properties diseases, infections, cancer.