For over a century, the brain has held the starring role in the story of how the body defends itself — but a team at Ohio State University is quietly rewriting that script. Funded by a $1.2 million grant from the W.M. Keck Foundation, neuroscientist Phillip Popovich and his colleagues are investigating whether the spinal cord possesses its own capacity to sense infection and direct immune response, independent of the brain's involvement. At the heart of this inquiry are newly discovered nerve cells — ISE neurons — that appear to awaken during inflammation, suggesting that the body's immune int
Ohio State Researchers Awarded $1.2M to Map Spinal Cord's Hidden Immune Role
That circuitry has been a black box. This project is our attempt to finally open it.
Mark
Why does it matter whether the spinal cord detects infection independently? Doesn't the brain ultimately control everything anyway?
Mimi
Because if the spinal cord can sense and respond to threats without waiting for the brain's permission, it changes the whole architecture of how immunity works. It's faster, more distributed, less centralized. And it explains why spinal cord injuries cripple immune function—you've severed a direct line of communication that the brain can't fully compensate for.
Mark
So these ISE neurons—they're completely new cells that nobody knew about before?
Mimi
Not entirely new cells, but a population that nobody had identified as having this specific function. They activate during inflammation in ways that suggest they're reading the body's immune state directly, not just relaying signals from above.
Mark
How do you actually prove that these neurons are causing the immune changes, not just responding to them?
Mimi
That's the third stage of the research. You turn them on and off in mice and watch what happens to the immune response. If you silence them and immunity suffers, or activate them and immunity improves, you've got your proof of causation.
Mark
What happens if they're right? What changes in medicine?
Mimi
You suddenly have a new target for treating inflammatory diseases. Instead of just trying to suppress the immune system broadly, you could potentially modulate how the spinal cord talks to immune cells. It's a completely different lever to pull.
Mark
And if they're wrong?
Mimi
Then the brain remains the primary controller, and we've learned something useful about the spinal cord's role in a system we thought we understood. Either way, you're opening a door that's been closed for a century.
Le Pouls
- A century-old assumption — that the brain alone governs immune response — is now under serious scientific scrutiny.
- Newly identified spinal cord neurons light up during inflammation, hinting at an entirely separate immune detection pathway that has gone unnoticed until now.
- Previous research showed that spinal cord injuries permanently impair immune function, but the specific neurons responsible and their mechanisms have remained a frustrating mystery.
- A three-phase investigation using genetic engineering, advanced imaging, and AI modeling aims to map, predict, and experimentally confirm which spinal neurons actually control immune behavior in mice.
- If the hypothesis holds, it could unlock new therapeutic targets for inflammatory diseases where the immune system turns against the body's own tissues.
For over a century, the brain has held the starring role in the story of how the body defends itself — but a team at Ohio State University is quietly rewriting that script. Funded by a $1.2 million grant from the W.M. Keck Foundation, neuroscientist Phillip Popovich and his colleagues are investigating whether the spinal cord possesses its own capacity to sense infection and direct immune response, independent of the brain's involvement. At the heart of this inquiry are newly discovered nerve cells — ISE neurons — that appear to awaken during inflammation, suggesting that the body's immune intelligence may be more distributed, and more democratic, than we ever imagined.
For more than a century, the brain has been cast as the command center of immunity — detecting threats, marshaling defenses, and coordinating the body's response to infection. Phillip Popovich, a neuroscience professor at Ohio State, believes that story leaves out a crucial character. With $1.2 million from the W.M. Keck Foundation, his team is now investigating whether the spinal cord doesn't merely carry messages between brain and body, but actively senses infection and directs immune responses on its own.
At the center of this inquiry is a previously unknown population of nerve cells his lab has identified in the spinal cord — immune synergy encoding neurons, or ISE neurons — which activate when inflammation spreads through the body. Their existence suggests the spinal cord may run its own immune detection system, entirely apart from the brain. Earlier work by Popovich's team had already established a link: spinal cord injuries, they found, permanently compromise immune function — a condition they named spinal cord injury-induced immune deficiency syndrome. But which neurons were responsible, and how they operated, remained unknown. "That circuitry has been a black box," Popovich said. This grant is the key to opening it.
The research proceeds in three stages. First, using imaging and genetically modified mice, the team will map which spinal neurons respond to infection and trace where their signals travel. Second, that data will train an AI model to identify which cells play the most critical roles in immune regulation. Third, researchers will selectively activate or silence those neurons to determine whether doing so measurably changes immune responses — moving from correlation to causation.
Popovich is joined by experts in bioinformatics, microbial immunity, and chronic brain injury, forming a team that is shifting its focus from what breaks when the spinal-immune connection fails to how it functions when healthy. Should their hypothesis prove out, the implications reach well beyond basic science — potentially revealing new drug targets for inflammatory diseases where the immune system turns destructive. For now, the work is exploratory, rooted in mice and mapping. But the underlying wager is a profound one: that the spinal cord has been quietly conversing with the immune system all along, and science is only now learning to listen.
For more than a century, neuroscientists have told a story about immunity that centers on the brain—how it detects threats, orchestrates defenses, talks to the body's immune cells. Phillip Popovich, a neuroscience professor at Ohio State, thinks that story is incomplete. The W.M. Keck Foundation has just awarded his team $1.2 million to test a different idea: that the spinal cord doesn't merely relay messages between brain and body, but actively senses infection and commands an immune response all on its own.
Popovich's lab has discovered a previously unknown population of nerve cells in the spinal cord, which they call immune synergy encoding neurons, or ISE neurons. These cells light up when inflammation spreads through the body—a finding that suggests the spinal cord may operate its own immune detection system, independent of the brain's involvement. "Our research suggests the spinal cord isn't just a cable carrying messages up to the brain and back," Popovich said. "It may have its own pathway for detecting infection and signaling the immune system without involving the brain."
The team's earlier work had already hinted at this possibility. They found that spinal cord injuries permanently damage immune function, a condition they call spinal cord injury-induced immune deficiency syndrome. That discovery established the spinal cord's importance to immunity, but left a crucial question unanswered: which specific neurons are responsible, and how do they work? "That circuitry has been a black box," Popovich explained. The new grant allows them to finally open it.
The research unfolds in three stages. First, the team will use imaging technology and genetic engineering to create a detailed map of which spinal cord nerve cells respond to infection or inflammation, and where those cells send their signals. They're working with genetically modified mice that allow researchers to permanently tag neurons the moment they react to an immune challenge, then trace exactly which cells activated and how they connect to one another. Second, they'll feed that mapping data into an artificial intelligence model designed to predict which nerve cells play the most critical roles in immune regulation. Third, they'll experimentally activate or deactivate those specific neurons in mice to determine whether doing so actually changes the animals' immune responses and behavior—the crucial step that proves causation rather than mere correlation.
Popovich leads the Belford Center for Spinal Cord Injury at Ohio State's Wexner Medical Center and holds the Ray W. Poppleton Research Designated Chair. He's joined on the project by Qin Ma, a bioinformatics expert and leader of the Immuno-Oncology Informatics group; Eugene Oltz, who chairs the Division of Microbial Infection and Immunity; and Andrea Tedeschi, an associate professor of neuroscience focused on chronic brain injury. Together, they're pivoting from studying what happens when the spinal-immune connection breaks to understanding how it functions when it's healthy.
If their hypothesis holds, the implications could reshape how scientists understand the nervous and immune systems' relationship. More immediately, it could open new avenues for treating inflammatory diseases—conditions where the immune system misfires and damages the body's own tissues. Understanding how the spinal cord detects and responds to infection might reveal new targets for drugs or interventions that could restore balance to dysregulated immune responses. For now, the work remains exploratory, grounded in mice and mapping. But Popovich's team is betting that the spinal cord has been whispering to the immune system all along, and nobody was listening.
Citations marquantes
The spinal cord may have its own pathway for detecting infection and signaling the immune system without involving the brain.— Phillip Popovich, Ohio State neuroscience professor
We spent decades documenting what happens when this system is broken. Now we're pivoting to map how it works when it's healthy.— Phillip Popovich
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