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

• Published in: Neuron (Cambridge, Mass.) Mass.), 2015-02, Vol.85 (4), p.703-709
• Main Authors: Gadani, Sachin P., Walsh, James T., Smirnov, Igor, Zheng, Jingjing, Kipnis, Jonathan
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animals; Animals, Newborn; Cells, Cultured; Central Nervous System Diseases - etiology; Central Nervous System Diseases - immunology; Central Nervous System Diseases - pathology; Central Nervous System Diseases - physiopathology; Colleges & universities; CX3C Chemokine Receptor 1; Disease Models, Animal; Female; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; In Vitro Techniques; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukins - genetics; Interleukins - metabolism; Ki-67 Antigen - metabolism; Male; Medical research; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins - metabolism; Neuroglia - metabolism; Neurons; Neurons - metabolism; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; Receptors, Interleukin - deficiency; Receptors, Interleukin - genetics; Recovery of Function - physiology; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; Rodents; Spinal cord
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2015.01.013

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 the innate 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 from damaged oligodendrocytes, acting on local astrocytes and microglia to induce chemokines critical for monocyte recruitment. Mice lacking IL-33 have impaired recovery after CNS injury, which is associated with reduced myeloid cell infiltrates and decreased induction of M2 genes at the injury site. These results demonstrate a novel molecular mediator contributing to immune cell recruitment to the injured CNS and may lead to new therapeutic insights in CNS injury and neurodegenerative diseases. •IL-33 is expressed in mature oligodendrocytes and gray matter astrocytes•IL-33 is released from injured CNS tissue•Mice lacking IL-33 have impaired recovery after CNS injury•IL-33 drives chemokine production critical for monocyte recruitment after SCI Gadani et al. characterized the cellular localization of interleukin (IL)-33 to oligodendrocytes and gray matter astrocytes in the healthy CNS. Using IL-33–/– mice, the authors show that IL-33 is critical to normal monocyte recruitment and recovery after CNS injury.