Disruption of E-Cadherin-Mediated Adhesion Induces a Functionally Distinct Pathway of Dendritic Cell Maturation

Aimin Jiang; Ona Bloom; Satoru Ono; Weiguo Cui; Juli Unternaehrer; Shan Jiang; J. Andrew Whitney; John Connolly; Jacques Banchereau; Ira Mellman

doi:10.1016/j.immuni.2007.08.015

Disruption of E-Cadherin-Mediated Adhesion Induces a Functionally Distinct Pathway of Dendritic Cell Maturation

Aimin Jiang, Ona Bloom, Satoru Ono, Weiguo Cui, Juli Unternaehrer, Shan Jiang, J. Andrew Whitney, John Connolly, Jacques Banchereau, Ira Mellman^*

^*Corresponding author for this work

Pathology

Research output: Contribution to journal › Article › peer-review

294 Scopus citations

Abstract

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 β-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.".

Original language	English (US)
Pages (from-to)	610-624
Number of pages	15
Journal	Immunity
Volume	27
Issue number	4
DOIs	https://doi.org/10.1016/j.immuni.2007.08.015
State	Published - Oct 26 2007

Funding

We thank C. Fu, H. Li, H. Rhee, C. Bergman, and members of the Mellarren group for technical help and discussion. We are grateful to X. Qian and Y. Zhou for help and to L. Bennett for validation in the microarray work. The use of real-time RT-PCR was supported by NIH grant AR46032. A.J. was supported by a Cancer Research Institute fellowship. This work was supported by the NIH (R37AI34098 and U19AI057234), the Sandler Family Foundation, and the Ludwig Institute for Cancer Research.

Keywords

CELLIMMUNO
MOLIMMUNO

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.immuni.2007.08.015

Cite this

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title = "Disruption of E-Cadherin-Mediated Adhesion Induces a Functionally Distinct Pathway of Dendritic Cell Maturation",

abstract = "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 β-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.{"}.",

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note = "Funding Information: We thank C. Fu, H. Li, H. Rhee, C. Bergman, and members of the Mellarren group for technical help and discussion. We are grateful to X. Qian and Y. Zhou for help and to L. Bennett for validation in the microarray work. The use of real-time RT-PCR was supported by NIH grant AR46032. A.J. was supported by a Cancer Research Institute fellowship. This work was supported by the NIH (R37AI34098 and U19AI057234), the Sandler Family Foundation, and the Ludwig Institute for Cancer Research. ",

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AU - Unternaehrer, Juli

AU - Jiang, Shan

AU - Whitney, J. Andrew

AU - Connolly, John

AU - Banchereau, Jacques

AU - Mellman, Ira

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PY - 2007/10/26

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N2 - 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 β-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.".

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Disruption of E-Cadherin-Mediated Adhesion Induces a Functionally Distinct Pathway of Dendritic Cell Maturation

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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