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Cross-Organ Neuroimmunology of Behavior

Xuanming Guo1, Scott J Russo1

  • 1Nash Family Department of Neuroscience; Brain-Body Research Institute; and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; email: xuanming.guo@mssm.edu, scott.russo@mssm.edu.

Annual Review of Immunology
|February 23, 2026
PubMed

Insights

The Cross-Organ Neuroimmunology of Behavior (CONB) Network views behavior as a whole-body immune-brain interaction. This framework links systemic health to brain function, offering new avenues for precision medicine.

Area of Science:

  • Neuroimmunology
  • Systems Biology
  • Behavioral Neuroscience

Background:

  • Neuroimmune communication involves cytokine-neural signaling, glial-immune interactions, and neuroendocrine pathways.
  • Peripheral organs act as crucial nodes in this communication network.
  • Understanding these interactions is key to deciphering complex behaviors.

Purpose of the Study:

  • Introduce the Cross-Organ Neuroimmunology of Behavior (CONB) Network framework.
  • Reconceptualize behavior as an emergent property of a distributed, whole-body immune-brain network.
  • Integrate knowledge of neuroimmune communication and peripheral organ signaling.

Main Methods:

  • Conceptual framework development.
  • Integration of existing knowledge on neuroimmune and neuroendocrine pathways.
  • Analysis of peripheral organ roles as network nodes.

Main Results:

  • Identified emergent network properties like degeneracy and hub organs.
  • Demonstrated how peripheral changes translate into systemic signals influencing the brain.
  • Linked complex behaviors to multisystem disease crosstalk.

Conclusions:

  • Reframed brain diseases as systemic network dysregulation.
  • Highlighted the CONB Network's potential for precision medicine through immune biomarkers.
  • Proposed recalibrating cross-organ neuroimmune networks for therapeutic strategies and restoring homeostasis.

Keywords:
adaptive immunitybrain–body interactionsinnate immunityneurological diseasepsychiatric diseasepsychoneuroimmunology

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