The Glia-Derived Alarmin IL-33 Orchestrates the Immune Response and Promotes Recovery following CNS Injury

Sachin P. Gadani, James T. Walsh, Igor Smirnov, Jingjing Zheng, Jonathan Kipnis

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

Abstract

Inflammation is a prominent feature of CNS injury that heavily influences neuronal survival, yet the signals that initiate and control it remain poorly understood. Here we identify the nuclear alarmin, interleukin (IL)-33, as an important regulator of theinnate immune response after CNS injury. IL-33 is expressed widely throughout the healthy brain and is concentrated in white mater due to predominant expression in post-mitotic oligodendrocytes. IL-33 is released immediately after CNS injury fromdamaged oligodendrocytes, acting on local astrocytes and microglia to induce chemokines critical for monocyte recruitment. Mice lacking IL-33 haveimpaired recovery after CNS injury, which isassociated with reduced myeloid cell infiltrates anddecreased induction of M2 genes at the injury site. These results demonstrate a novel molecular mediator contributing to immune cell recruitment tothe injured CNS and may lead to new therapeuticinsights in CNS injury and neurodegenerative diseases.

Original languageEnglish
Pages (from-to)703-709
Number of pages7
JournalNeuron
Volume85
Issue number4
DOIs
StatePublished - Feb 18 2015
Externally publishedYes

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