TY - JOUR
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
N1 - Funding Information:
We thank the members of the J.K. lab for their valuable comments during multiple discussions of this work. This work was primarily supported by a grant from the National Institute of Neurological Disorders and Stroke, NIH (NS061973 award to J.K.).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/2/18
Y1 - 2015/2/18
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84924988052&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2015.01.013
DO - 10.1016/j.neuron.2015.01.013
M3 - Article
C2 - 25661185
AN - SCOPUS:84924988052
SN - 0896-6273
VL - 85
SP - 703
EP - 709
JO - Neuron
JF - Neuron
IS - 4
ER -