Dab2, a negative regulator of DC immunogenicity, is an attractive molecular target for DC-based immunotherapy

Md Selim Ahmed; Se Eun Byeon; Yideul Jeong; Mohammad Alam Miah; Md Salahuddin; Yoon Lee; Sung Soo Park; Yong Soo Bae

doi:10.4161/2162402X.2014.984550

Dab2, a negative regulator of DC immunogenicity, is an attractive molecular target for DC-based immunotherapy

Md Selim Ahmed, Se Eun Byeon, Yideul Jeong, Mohammad Alam Miah, Md Salahuddin, Yoon Lee, Sung Soo Park, Yong Soo Bae

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

33 Citations (Scopus)

Abstract

Dab2 is an adapter protein involved in receptor-mediated signaling, endocytosis, cell adhesion, hematopoietic cell differentiation, and angiogenesis. It plays a pivotal role in controlling cellular homeostasis. In the immune system, the Dab2 is a Foxp3 target gene and is required for regulatory T (Treg) cell function. Dab2 expression and its biological function in dendritic cells (DCs) have not been described. In this study, we found that Dab2 was significantly induced during the development of mouse bone marrow (BM)-derived DCs (BMDCs) and human monocyte-derived DCs (MoDCs). Even in a steady state, Dab2 was expressed in mouse splenic DCs (spDCs). STAT5 activation, Foxp3 expression, and hnRNPE1 activation mediated by PI3K/Akt signaling were required for Dab2 expression during GM-CSF-derived BMDC development regardless of TGF-β signaling. Dab2-silencing was accompanied by enhanced IL-12 and IL-6 expression, and an improved capacity of DC for antigen uptake, migration and T cell stimulation, which generated strong CTL in vaccinated mice. Vaccination with Dab2-silenced DCs inhibited tumor growth more effectively than did vaccination with wild type DCs. Dab2-overexpression abrogated the efficacy of the DC vaccine in DC-based tumor immunotherapy. These data strongly suggest that Dab2 might be an intrinsic negative regulator of the immunogenicity of DCs, thus might be an attractive molecular target to improve DC vaccine efficacy.

Original language	English
Pages (from-to)	984550
Number of pages	1
Journal	OncoImmunology
Volume	4
Issue number	1
DOIs	https://doi.org/10.4161/2162402X.2014.984550
Publication status	Published - 2015 Jan 2

Bibliographical note

Funding Information:
This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean Ministry of Education Science and Technology (2012M3A9B402826), and in part by the Bio New Drug Grants (A102130 and A110054) from the Korean Ministry of Health and Welfare.

Publisher Copyright:
© 2015 Taylor & Francis Group, LLC.

Keywords

Dab2
dendritic cells
immunogenicity
molecular target

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Oncology

UN SDGs

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

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10.4161/2162402X.2014.984550

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title = "Dab2, a negative regulator of DC immunogenicity, is an attractive molecular target for DC-based immunotherapy",

abstract = "Dab2 is an adapter protein involved in receptor-mediated signaling, endocytosis, cell adhesion, hematopoietic cell differentiation, and angiogenesis. It plays a pivotal role in controlling cellular homeostasis. In the immune system, the Dab2 is a Foxp3 target gene and is required for regulatory T (Treg) cell function. Dab2 expression and its biological function in dendritic cells (DCs) have not been described. In this study, we found that Dab2 was significantly induced during the development of mouse bone marrow (BM)-derived DCs (BMDCs) and human monocyte-derived DCs (MoDCs). Even in a steady state, Dab2 was expressed in mouse splenic DCs (spDCs). STAT5 activation, Foxp3 expression, and hnRNPE1 activation mediated by PI3K/Akt signaling were required for Dab2 expression during GM-CSF-derived BMDC development regardless of TGF-β signaling. Dab2-silencing was accompanied by enhanced IL-12 and IL-6 expression, and an improved capacity of DC for antigen uptake, migration and T cell stimulation, which generated strong CTL in vaccinated mice. Vaccination with Dab2-silenced DCs inhibited tumor growth more effectively than did vaccination with wild type DCs. Dab2-overexpression abrogated the efficacy of the DC vaccine in DC-based tumor immunotherapy. These data strongly suggest that Dab2 might be an intrinsic negative regulator of the immunogenicity of DCs, thus might be an attractive molecular target to improve DC vaccine efficacy.",

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author = "Ahmed, {Md Selim} and Byeon, {Se Eun} and Yideul Jeong and Miah, {Mohammad Alam} and Md Salahuddin and Yoon Lee and Park, {Sung Soo} and Bae, {Yong Soo}",

note = "Funding Information: This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean Ministry of Education Science and Technology (2012M3A9B402826), and in part by the Bio New Drug Grants (A102130 and A110054) from the Korean Ministry of Health and Welfare. Publisher Copyright: {\textcopyright} 2015 Taylor & Francis Group, LLC.",

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T1 - Dab2, a negative regulator of DC immunogenicity, is an attractive molecular target for DC-based immunotherapy

AU - Ahmed, Md Selim

AU - Byeon, Se Eun

AU - Jeong, Yideul

AU - Miah, Mohammad Alam

AU - Salahuddin, Md

AU - Lee, Yoon

AU - Park, Sung Soo

AU - Bae, Yong Soo

N1 - Funding Information: This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean Ministry of Education Science and Technology (2012M3A9B402826), and in part by the Bio New Drug Grants (A102130 and A110054) from the Korean Ministry of Health and Welfare. Publisher Copyright: © 2015 Taylor & Francis Group, LLC.

PY - 2015/1/2

Y1 - 2015/1/2

N2 - Dab2 is an adapter protein involved in receptor-mediated signaling, endocytosis, cell adhesion, hematopoietic cell differentiation, and angiogenesis. It plays a pivotal role in controlling cellular homeostasis. In the immune system, the Dab2 is a Foxp3 target gene and is required for regulatory T (Treg) cell function. Dab2 expression and its biological function in dendritic cells (DCs) have not been described. In this study, we found that Dab2 was significantly induced during the development of mouse bone marrow (BM)-derived DCs (BMDCs) and human monocyte-derived DCs (MoDCs). Even in a steady state, Dab2 was expressed in mouse splenic DCs (spDCs). STAT5 activation, Foxp3 expression, and hnRNPE1 activation mediated by PI3K/Akt signaling were required for Dab2 expression during GM-CSF-derived BMDC development regardless of TGF-β signaling. Dab2-silencing was accompanied by enhanced IL-12 and IL-6 expression, and an improved capacity of DC for antigen uptake, migration and T cell stimulation, which generated strong CTL in vaccinated mice. Vaccination with Dab2-silenced DCs inhibited tumor growth more effectively than did vaccination with wild type DCs. Dab2-overexpression abrogated the efficacy of the DC vaccine in DC-based tumor immunotherapy. These data strongly suggest that Dab2 might be an intrinsic negative regulator of the immunogenicity of DCs, thus might be an attractive molecular target to improve DC vaccine efficacy.

AB - Dab2 is an adapter protein involved in receptor-mediated signaling, endocytosis, cell adhesion, hematopoietic cell differentiation, and angiogenesis. It plays a pivotal role in controlling cellular homeostasis. In the immune system, the Dab2 is a Foxp3 target gene and is required for regulatory T (Treg) cell function. Dab2 expression and its biological function in dendritic cells (DCs) have not been described. In this study, we found that Dab2 was significantly induced during the development of mouse bone marrow (BM)-derived DCs (BMDCs) and human monocyte-derived DCs (MoDCs). Even in a steady state, Dab2 was expressed in mouse splenic DCs (spDCs). STAT5 activation, Foxp3 expression, and hnRNPE1 activation mediated by PI3K/Akt signaling were required for Dab2 expression during GM-CSF-derived BMDC development regardless of TGF-β signaling. Dab2-silencing was accompanied by enhanced IL-12 and IL-6 expression, and an improved capacity of DC for antigen uptake, migration and T cell stimulation, which generated strong CTL in vaccinated mice. Vaccination with Dab2-silenced DCs inhibited tumor growth more effectively than did vaccination with wild type DCs. Dab2-overexpression abrogated the efficacy of the DC vaccine in DC-based tumor immunotherapy. These data strongly suggest that Dab2 might be an intrinsic negative regulator of the immunogenicity of DCs, thus might be an attractive molecular target to improve DC vaccine efficacy.

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KW - molecular target

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VL - 4

SP - 984550

JO - OncoImmunology

JF - OncoImmunology

IS - 1

ER -

Dab2, a negative regulator of DC immunogenicity, is an attractive molecular target for DC-based immunotherapy

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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