Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation

The maturation of dendritic cells (DCs) after exposureto microbial products or inflammatory mediators plays a critical role in initiating the immune response. We found that maturation can also occur under steady-state conditions triggered by alterations in E-cadherin-mediate DC-DC adhesion. Selective disruption of these interactions induced the typical features of DC maturation including the upregulation of costimulatory molecules, MHC class 11, and chemokine receptors. These events were triggered at least in part by activation of the P-catenin pathway. However, unlike maturation induced by microbial products, E-cadherin-stimulated DCs failed to release immunostimulatory cytokines, exhibiting an entirely different transcriptional profile. As a result, E-cadherin-stimulated DCs elicited an entirely different T cell response in vivo, generating T cells with a regulatory as opposed to an effector phenotype. These I)Cs induced tolerance in vivo and may thus contribute to the elusive steady-state tolerogenic DCs.