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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Bibliographic Details
Published in:Journal of immunology research 2018-01, Vol.2018 (2018), p.1-8
Main Authors: Ohl, Kim, Tenbrock, Klaus, Schippers, Anastasia
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation
Antigens
Autoimmune diseases
Autoimmune Diseases - immunology
B-Lymphocytes - physiology
CD11c antigen
CD11c Antigen - metabolism
Cell activation
Cell proliferation
Cells, Cultured
Clonal deletion
Cyclic AMP response element-binding protein
Cyclic AMP Response Element-Binding Protein - genetics
Cyclic AMP Response Element-Binding Protein - metabolism
Cytokines
Dendritic cells
Dendritic Cells - immunology
Flow cytometry
Gene deletion
Germinal Center - immunology
Germinal centers
Homeostasis
Immune response
Immunization
Immunoglobulin G - blood
Immunological tolerance
Immunology
Kinases
Lymphocyte Activation
Lymphocytes
Lymphocytes B
Lymphocytes T
Macrophages
Medicine
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular chains
Proteins
T cell receptors
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Summary: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.
ISSN:2314-8861
2314-7156
DOI:10.1155/2018/8947230