Computational inference of chemokine-mediated roles for the vagus nerve in modulating intra- and inter-tissue inflammation

Ashti M. Shah, Ruben Zamora, Derek Barclay, Jinling Yin, Fayten El-Dehaibi, Meghan Addorisio, Tea Tsaava, Aisling Tynan, Kevin Tracey, Sangeeta S. Chavan, Yoram Vodovotz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Introduction: The vagus nerve innervates multiple organs, but its role in regulating cross-tissue spread of inflammation is as yet unclear. We hypothesized that the vagus nerve may regulate cross-tissue inflammation via modulation of the putatively neurally regulated chemokine IP-10/CXCL10. Methods: Rate-of-change analysis, dynamic network analysis, and dynamic hypergraphs were used to model intra- and inter-tissue trends, respectively, in inflammatory mediators from mice that underwent either vagotomy or sham surgery. Results: This analysis suggested that vagotomy primarily disrupts the cross-tissue attenuation of inflammatory networks involving IP-10 as well as the chemokines MIG/CXCL9 and CCL2/MCP-1 along with the cytokines IFN-γ and IL-6. Computational analysis also suggested that the vagus-dependent rate of expression of IP-10 and MIG/CXCL9 in the spleen impacts the trajectory of chemokine expression in other tissues. Perturbation of this complex system with bacterial lipopolysaccharide (LPS) revealed a vagally regulated role for MIG in the heart. Further, LPS-stimulated expression of IP-10 was inferred to be vagus-independent across all tissues examined while reducing connectivity to IL-6 and MCP-1, a hypothesis supported by Boolean network modeling. Discussion: Together, these studies define novel spatiotemporal dimensions of vagus-regulated acute inflammation.

Original languageEnglish
Article number1266279
JournalFrontiers in Systems Biology
Volume4
DOIs
StatePublished - 2024
Externally publishedYes

Keywords

  • chemokines
  • inflammation
  • systems biology
  • vagotomy
  • vagus nerve

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