Abstract
C/EBP beta is considered a key element of interleukin-6 (IL-6) signalling as well as an important transcriptional regulator of the IL-6 gene itself. We describe here how mice lacking C/EBP beta develop a pathology similar to mice overexpressing IL-6 and nearly identical to multicentric Castleman's disease in human patients, with marked splenomegaly, peripheral lymphadenopathy and enhanced haemopoiesis. Humoral, innate and cellular immunity are also profoundly distorted, as shown by the defective activation of splenic macrophages, the strong impairement of IL-12 production, the increased susceptibility to Candida albicans infection and the altered T-helper function. Our data show that C/EBP beta is crucial for the correct functional regulation and homeostatic control of haemopoietic and lymphoid compartments.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Fungal / biosynthesis
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CCAAT-Enhancer-Binding Proteins
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CD4-Positive T-Lymphocytes / immunology*
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Candidiasis / etiology
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Castleman Disease / etiology
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Castleman Disease / genetics
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Castleman Disease / immunology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology*
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Disease Models, Animal
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Female
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Humans
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Interleukin-6 / blood
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Interleukin-6 / genetics
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Lymphoproliferative Disorders / etiology*
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Lymphoproliferative Disorders / genetics
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Lymphoproliferative Disorders / immunology
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Macrophage Activation
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Male
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Mice
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Mice, Mutant Strains
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Myeloproliferative Disorders / etiology
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Myeloproliferative Disorders / genetics
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Myeloproliferative Disorders / immunology
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Nitric Oxide / biosynthesis
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Nuclear Proteins / genetics
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Nuclear Proteins / immunology*
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Spleen / immunology
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Spleen / pathology
Substances
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Antibodies, Fungal
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CCAAT-Enhancer-Binding Proteins
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DNA-Binding Proteins
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Interleukin-6
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Nuclear Proteins
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Nitric Oxide