Recent research has unveiled a compelling connection between the immune system and brain behavior, highlighting how a single immune molecule, interleukin-17 (IL-17), can influence both anxiety and sociability depending on its site of action in the brain. This discovery sheds light on the intricate interplay between our immune responses and emotional states, offering potential avenues for therapeutic interventions in conditions like autism and anxiety.
Dual Roles of IL-17 in the Brain
IL-17, traditionally recognized for its role in combating infections by regulating inflammation and guiding immune cell activity, has now been implicated in modulating brain function. Scientists from MIT and Harvard Medical School have demonstrated that IL-17 acts on two distinct brain regions with contrasting effects: the amygdala and the somatosensory cortex.
In the amygdala, a region associated with processing emotions such as fear and anxiety, IL-17 increases neuronal excitability, leading to heightened anxiety levels. Conversely, in the somatosensory cortex, which is involved in processing sensory information and social behavior, IL-17 reduces neuronal excitability, promoting sociability.
The Fever Effect and Autism
The interest in IL-17’s role in behavior was piqued by observations of the “fever effect” in autistic children, where behavioral symptoms temporarily improve during febrile episodes. In a 2019 study, researchers found that in mice, IL-17 released during infection suppressed activity in a specific cortical region known as S1DZ. Overactivation of neurons in this area had been linked to autism-like behaviors, including repetitive actions and reduced social interaction.
Mapping IL-17 Receptors in the Brain
IL-17 exists in six forms and interacts with five different receptors. The researchers mapped the expression of these receptors across the brain, discovering that IL-17RA and IL-17RB are present in the cortex, including the S1DZ region. These receptors are located on neurons that receive proprioceptive input and are involved in controlling behavior. When IL-17E binds to these receptors, it reduces neuronal excitability, leading to increased sociability.
IL-17 as a Neuromodulator
Interestingly, IL-17E appears to function similarly to a neuromodulator, substances that regulate neuron activity. This suggests that IL-17 may have originally evolved to modulate brain function and was later co-opted by the immune system to aid in inflammation. Supporting this, studies in the worm C. elegans show that IL-17 influences social behavior without playing a role in immunity. Additionally, in mammals, IL-17E is produced by neurons in the cortex, including the S1DZ region.
Anxiety Induction in the Amygdala
Further investigations revealed that IL-17RA and IL-17RE receptors are expressed in the basolateral amygdala (BLA), a region critical for emotional processing. When IL-17A and IL-17C bind to these receptors, they increase neuronal excitability, resulting in heightened anxiety. This mechanism may serve an adaptive purpose during illness, encouraging individuals to isolate and prevent the spread of infection.
Implications for Treatment
These findings underscore the potential of targeting the immune system to influence brain function. By understanding how IL-17 and its receptors operate in different brain regions, researchers hope to develop immune-based therapies for neurological conditions such as autism and depression. This approach could offer a novel pathway for treatment, focusing on modulating immune responses rather than directly targeting the brain.
Conclusion
The discovery of IL-17’s dual role in modulating anxiety and sociability highlights the complex relationship between the immune system and brain behavior. As research continues to unravel these connections, it opens the door to innovative treatments that harness the immune system’s influence on the brain, potentially transforming our approach to mental health disorders.
