An immune receptor in neurons shapes social behavior, and a $2.4M NIH grant will map how

For decades, interleukin-1 receptor type 1 (IL-1R1) has been studied almost exclusively as an immune system component, a receptor that helps orchestrate inflammatory responses when the body fights infection. That it also appears on certain neurons was known but largely dismissed as a footnote. Now, research from Florida Atlantic University suggests that footnote may be one of the most important untold stories in neuroscience.

The National Institutes of Health has awarded FAU $2.4 million to investigate what IL-1R1 actually does in neurons. The grant, funded by the NIH's National Institute of Neurological Disorders and Stroke, supports a project led by Ning Quan in the Department of Biomedical Science at FAU's Charles E. Schmidt College of Medicine.

An immune receptor with a day job in the brain

Quan's previous work established that neuronal IL-1R1 is essential for behavioral changes caused by chronic social stress. That was a surprising finding: an immune receptor driving behavioral responses suggested that the traditional separation between immune signaling and neural communication might be artificial.

The new grant will fund a systematic investigation of where and when IL-1R1 is expressed in the brain, how its expression changes with experience, and how it influences communication between neurons. A particular focus will be hippocampal circuits involved in social discrimination, the brain's ability to distinguish between familiar and unfamiliar individuals, a fundamental component of normal social interaction.

Circuit-level effects from single-cell expression

One of the most intriguing preliminary findings is that the receptor's influence extends beyond the neurons that express it. Neurons carrying IL-1R1 can alter the activity and plasticity of neighboring neurons that do not have the receptor themselves, provided the two cells are directly connected through synapses.

This means IL-1R1 operates at the level of neural circuits rather than individual cells. A single receptor-expressing neuron can effectively modulate the behavior of an entire local network. This is a fundamentally different model from the traditional view, where immune receptors on neurons were assumed to simply make those specific cells responsive to inflammatory signals.

Implications for autism and psychiatric disorders

If IL-1R1 actively shapes how synapses form and how circuits reorganize in response to experience, it sits squarely at the intersection of immune function and neurodevelopment. Disruptions in social behavior and circuit development are hallmarks of autism spectrum disorder, schizophrenia, and other psychiatric and neurodevelopmental conditions.

Randy Blakely, executive director of FAU's Stiles-Nicholson Brain Institute and a co-investigator on the grant, noted that the work opens new conceptual pathways for understanding disorders where brain networks and social behaviors are disrupted. Rather than targeting symptoms, interventions informed by this research could target the circuit dysfunction itself.

What the grant will fund

The project will combine molecular biology, electrophysiology, and behavioral testing to build a comprehensive picture of neuronal IL-1R1 function. The researchers will map the receptor's expression across brain regions at different developmental stages, measure how experience (particularly social experience) changes that expression, and test how manipulating the receptor affects synaptic transmission and circuit remodeling.

Collaborator Jenny Wie, an associate professor in FAU's Department of Biomedical Science, will contribute to the project.

Early-stage research with long-term potential

This is basic science research, not drug development. The project aims to define the physiological role of a receptor whose function in the brain has remained unexplored for decades. Translating findings into therapeutic targets for psychiatric disorders would require additional years of research, including validation in human systems.

But the conceptual shift is significant. If the immune system and the nervous system communicate through shared molecular machinery at the synaptic level, the implications extend far beyond IL-1R1. It would mean that the tools we use to study and treat immune disorders and the tools we use for neurological conditions may need to converge.