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

作者：Smith Dirk E^*; Lipsky Brian P; Russell Chris; Ketchem Randal R; Kirchner Jacqueline; Hensley Kelly; Huang Yangyang; Friedman Wilma J; Boissonneault Vincent; Plante Marie Michele; Rivest Serge; Sims John E

来源：Immunity, 2009, 30(6): 817-831.

DOI：10.1016/j.immuni.2009.03.020

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 wildtype 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.

• 出版日期2009-6-19