Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation. Immunity 2007 Oct;27(4):610-24
Date
10/16/2007Pubmed ID
17936032Pubmed Central ID
PMC2151979DOI
10.1016/j.immuni.2007.08.015Scopus ID
2-s2.0-35348968837 (requires institutional sign-in at Scopus site) 289 CitationsAbstract
The maturation of dendritic cells (DCs) after exposure to 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-mediated DC-DC adhesion. Selective disruption of these interactions induced the typical features of DC maturation including the upregulation of costimulatory molecules, MHC class II, and chemokine receptors. These events were triggered at least in part by activation of the beta-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 DCs induced tolerance in vivo and may thus contribute to the elusive steady-state "tolerogenic DCs."
Author List
Jiang A, Bloom O, Ono S, Cui W, Unternaehrer J, Jiang S, Whitney JA, Connolly J, Banchereau J, Mellman IMESH terms used to index this publication - Major topics in bold
Adoptive TransferAnimals
Antigen Presentation
Blotting, Western
Cadherins
Cell Adhesion
Cell Communication
Cell Differentiation
Cells, Cultured
Dendritic Cells
Encephalomyelitis, Autoimmune, Experimental
Flow Cytometry
Fluorescent Antibody Technique
Gene Expression
Gene Expression Regulation
Humans
Immune Tolerance
Immunoprecipitation
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Protein Array Analysis
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes
TCF Transcription Factors
beta Catenin