A Central Nervous System-Restricted Isoform of the Interleukin-1 Receptor Accessory Protein Modulates Neuronal Responses to Interleukin-1

Interleukin-1 (IL-1) has multiple functions in both the periphery and the central nervous system (CNS) and is regulated at many levels. We identified an isoform of the IL-1 receptor (IL-1R) accessory protein (termed AcPb) that is expressed exclusively in the CNS. AcPb interacted with IL-1 and the IL...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2009-06, Vol.30 (6), p.817-831
Main Authors: Smith, Dirk E., Lipsky, Brian P., Russell, Chris, Ketchem, Randal R., Kirchner, Jacqueline, Hensley, Kelly, Huang, Yangyang, Friedman, Wilma J., Boissonneault, Vincent, Plante, Marie-Michèle, Rivest, Serge, Sims, John E.
Format: Article
Language:English
Subjects:
Alternative Splicing
Amino Acid Sequence
Animals
Arthritis
Astrocytes - immunology
Base Sequence
Brain - cytology
Brain - immunology
Brain research
Cell Line, Tumor
Cells, Cultured
Central Nervous System - immunology
Cytokines - immunology
Cytokines - metabolism
Gene expression
Humans
Inflammation - immunology
Interleukin-1 - metabolism
Interleukin-1 Receptor Accessory Protein - chemistry
Interleukin-1 Receptor Accessory Protein - genetics
Interleukin-1 Receptor Accessory Protein - metabolism
Medical research
Mice
Mice, Knockout
Molecular Sequence Data
MOLIMMUNO
Neurons - immunology
Protein Isoforms - chemistry
Protein Isoforms - genetics
Protein Isoforms - metabolism
Proteins
Rodents
Signal Transduction - immunology
Spinal cord
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Summary:Interleukin-1 (IL-1) has multiple functions in both the periphery and the central nervous system (CNS) and is regulated at many levels. We identified an isoform of the IL-1 receptor (IL-1R) accessory protein (termed AcPb) that is expressed exclusively in the CNS. AcPb interacted with IL-1 and the IL-1R but was unable to mediate canonical IL-1 responses. AcPb expression, however, modulated neuronal gene expression in response to IL-1 treatment in vitro. Animals lacking AcPb demonstrated an intact peripheral IL-1 response and developed experimental autoimmune encephalomyelitis (EAE) similarly to wild-type mice. AcPb-deficient mice were instead more vulnerable to local inflammatory challenge in the CNS and suffered enhanced neuronal degeneration as compared to AcP-deficient or wild-type mice. These findings implicate AcPb as an additional component of the highly regulated IL-1 system and suggest that it may play a role in modulating CNS responses to IL-1 and the interplay between inflammation and neuronal survival.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2009.03.020