Stress-induced red nucleus attenuation induces anxiety-like behavior and lymph node CCL5 secretion

Area of Science:

• Neuroimmunology
• Stress Neuroscience
• Psychoneuroimmunology

Background:

• Brain activity's control over immune responses in lymphoid organs is speculated but not fully understood.
• The specific brain regions and mechanisms linking stress, lymphoid organs, and anxiety remain elusive.
• Understanding the brain-lymph node axis is crucial for comprehending stress-induced behaviors.

Purpose of the Study:

• To identify the upstream brain regions controlling lymphoid organs during stress.
• To elucidate the neural pathways involved in stress-induced anxiety-like behavior.
• To investigate the role of CCL5 in the brain-lymph node communication during stress.

Main Methods:

• Analysis of CCL5 levels in stressed human participants and rat models.
• Retrograde tracing from cervical lymph nodes (CLN) to identify neuronal populations.
• Utilizing ablation and chemogenetic/pharmacogenetic manipulation of identified neurons in rats.
• Investigating the effects of modulating the primary motor cortex to red nucleus (RN) projection.

Main Results:

• CCL5 levels are elevated in stressed individuals and primarily produced in CLNs.
• Glutamatergic neurons in the red nucleus (RN) are identified as key players, with their activity correlating with CCL5 levels and anxiety.
• Inhibition of RN neurons exacerbates anxiety and CCL5 expression, while activation reduces them.
• Modulating the primary motor cortex to RN pathway impacts anxiety and CCL5 synthesis.

Conclusions:

• A novel brain-lymph node axis involving the red nucleus and CCL5 is identified.
• Lymphoid organs, specifically CLNs, function as stress-responsive endocrine organs.
• This axis provides critical insights into the neuro-immune mechanisms underlying stress and anxiety.