MD/PhD student Sachin Gadani, from the Kipnis Lab, recently discovered a protein, Interleukin-33 (IL-33), found to be significant in the central nervous system’s response to injury.
Gadani’s findings were published in a paper titled “The Glia-Derived Alarmin IL-33 Orchestrates the Immune Response and Promotes Recovery following CNS Injury” in the journal “Neuron” last month.
Interleukins are cytokines — molecules secreted by cells that act as chemical messengers for the immune system and participate in intercellular communication — according to the National Institute of Allergies and Infectious Diseases. There are approximately 34 different interleukin
proteins currently known, according to Gadani, but each is unique in function.
“Interleukin-33 is highly expressed in skin and the lung which are both barrier tissues as they separate the outside environment,” Gadani said. “What’s been shown is that after an injury, so if you were to cut your finger for example, IL-33 will be released from cell bodies of injured cells, and it reports cell damage to neighboring cells, initiating the immune response.”
Gadani wanted to determine whether IL-33 initiated the immune response in injuries that affect the central nervous system, when released. The first step was to find the site of IL-33. He and his team found that the molecule was expressed in oligodendrocytes — glial, or support cells, of the central nervous system that function to produce myelin, an insulating sheath applied to axons to allow faster conduction of nerve impulses.
“The next logical question is, what is [IL-33] doing there? Is it acting as an alarm signal?” Gadani said.
The most convincing experiments Gadani and his team performed involved inducing spinal cord injuries in mice and measuring levels of IL-33 in the cerebrospinal fluid — a clear body fluid produced in the brain that cushions and protects the central nervous system. These experiments suggested IL-33 was being released in response to injury.
Gadani explained that when tissue in the central nervous system is damaged, the damage can propagate over days, and this is where IL-33 is important.
“After injury, you have a lot of axons injured by the physical trauma, but over a few days you
have a spreading of the injury and more neurons that weren’t harmed by the initial trauma will die,” said Gadani. “The expansion of the injury site can be quite large. This is caused by a whole host of factors like cytotoxicity [and] lack of neurotrophic support, [and] the whole system is paralyzed.”
The next step is to better understand the role of IL-33. Gadani said he believes that IL-33, in bringing in macrophages, promotes neuroprotection.
“So far, we’ve shown where it’s expressed and that it’s important in recruiting cells. An important question is what [it is] doing in healthy oligodendrocytes — is there a role for it there without injury?” Gadani said.
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