CD11c-Specific Deletion Reveals CREB as a Critical Regulator of DC Function during the Germinal Center Response

Dendritic cells (DCs) are crucial for the balance between immune response and tolerance, but the molecular mechanism regulating development, differentiation, and homeostasis are poorly understood. The transcriptional activator CREB is involved in regulating different cells of the innate and adaptive...

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Main Authors: Kim Ohl, Anastasia Schippers, Klaus Tenbrock
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2018/8947230
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author Kim Ohl
Anastasia Schippers
Klaus Tenbrock
author_facet Kim Ohl
Anastasia Schippers
Klaus Tenbrock
author_sort Kim Ohl
collection DOAJ
description Dendritic cells (DCs) are crucial for the balance between immune response and tolerance, but the molecular mechanism regulating development, differentiation, and homeostasis are poorly understood. The transcriptional activator CREB is involved in regulating different cells of the innate and adaptive immune system and is a transcriptional regulator of development, survival, activation, or proliferation in macrophages, dendritic cells, B cells, and T cells. To directly examine the role of CREB in the regulation of DCs, the CREB gene was targeted for deletion with a CD11c-cre transgene. The deletion of CREB in CD11c+ cells did not involve any developmental or systemic defects within DC populations. However, CREB deficiency in CD11c+ cells reduced germinal center (GC) B cells in steady state, and immunization with NP-CGG resulted in a reduced formation of GCs, paralleled by the reduced production of IgGs in sera of immunized mice. In conclusion, we demonstrate that CREB expression in CD11c+ cells enhances germinal center responses, most likely by altering DC function, which might have implications for autoimmune diseases that are associated with dysregulated GC responses.
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spelling doaj-art-e786967b12404c9e80fd8541e28098db2025-08-20T03:26:10ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/89472308947230CD11c-Specific Deletion Reveals CREB as a Critical Regulator of DC Function during the Germinal Center ResponseKim Ohl0Anastasia Schippers1Klaus Tenbrock2Department of Pediatrics, Medical Faculty, RWTH Aachen, Aachen, GermanyDepartment of Pediatrics, Medical Faculty, RWTH Aachen, Aachen, GermanyDepartment of Pediatrics, Medical Faculty, RWTH Aachen, Aachen, GermanyDendritic cells (DCs) are crucial for the balance between immune response and tolerance, but the molecular mechanism regulating development, differentiation, and homeostasis are poorly understood. The transcriptional activator CREB is involved in regulating different cells of the innate and adaptive immune system and is a transcriptional regulator of development, survival, activation, or proliferation in macrophages, dendritic cells, B cells, and T cells. To directly examine the role of CREB in the regulation of DCs, the CREB gene was targeted for deletion with a CD11c-cre transgene. The deletion of CREB in CD11c+ cells did not involve any developmental or systemic defects within DC populations. However, CREB deficiency in CD11c+ cells reduced germinal center (GC) B cells in steady state, and immunization with NP-CGG resulted in a reduced formation of GCs, paralleled by the reduced production of IgGs in sera of immunized mice. In conclusion, we demonstrate that CREB expression in CD11c+ cells enhances germinal center responses, most likely by altering DC function, which might have implications for autoimmune diseases that are associated with dysregulated GC responses.http://dx.doi.org/10.1155/2018/8947230
spellingShingle Kim Ohl
Anastasia Schippers
Klaus Tenbrock
CD11c-Specific Deletion Reveals CREB as a Critical Regulator of DC Function during the Germinal Center Response
Journal of Immunology Research
title CD11c-Specific Deletion Reveals CREB as a Critical Regulator of DC Function during the Germinal Center Response
title_full CD11c-Specific Deletion Reveals CREB as a Critical Regulator of DC Function during the Germinal Center Response
title_fullStr CD11c-Specific Deletion Reveals CREB as a Critical Regulator of DC Function during the Germinal Center Response
title_full_unstemmed CD11c-Specific Deletion Reveals CREB as a Critical Regulator of DC Function during the Germinal Center Response
title_short CD11c-Specific Deletion Reveals CREB as a Critical Regulator of DC Function during the Germinal Center Response
title_sort cd11c specific deletion reveals creb as a critical regulator of dc function during the germinal center response
url http://dx.doi.org/10.1155/2018/8947230
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AT klaustenbrock cd11cspecificdeletionrevealscrebasacriticalregulatorofdcfunctionduringthegerminalcenterresponse