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

doi:10.1016/j.neuron.2015.01.013

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 journal › Article › peer-review

298 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 language	English
Pages (from-to)	703-709
Number of pages	7
Journal	Neuron
Volume	85
Issue number	4
DOIs	https://doi.org/10.1016/j.neuron.2015.01.013
State	Published - Feb 18 2015

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10.1016/j.neuron.2015.01.013

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

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.",

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T1 - The Glia-Derived Alarmin IL-33 Orchestrates the Immune Response and Promotes Recovery following CNS Injury

AU - Gadani, Sachin P.

AU - Walsh, James T.

AU - Smirnov, Igor

AU - Zheng, Jingjing

AU - Kipnis, Jonathan

PY - 2015/2/18

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AB - 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.

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

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