Computational inference of chemokine-mediated roles for the vagus nerve in modulating intra- and inter-tissue inflammation
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:...
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| Format: | Article |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Systems Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fsysb.2024.1266279/full |
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| author | Ashti M. Shah Ruben Zamora Ruben Zamora Derek Barclay Jinling Yin Fayten El-Dehaibi Meghan Addorisio Tea Tsaava Aisling Tynan Kevin Tracey Sangeeta S. Chavan Yoram Vodovotz Yoram Vodovotz |
| author_facet | Ashti M. Shah Ruben Zamora Ruben Zamora Derek Barclay Jinling Yin Fayten El-Dehaibi Meghan Addorisio Tea Tsaava Aisling Tynan Kevin Tracey Sangeeta S. Chavan Yoram Vodovotz Yoram Vodovotz |
| author_sort | Ashti M. Shah |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T00:50:51Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2674-0702 |
| language | English |
| last_indexed | 2025-03-21T00:17:54Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Systems Biology |
| spelling | doaj.art-496c8d0e4a73410d9d08b91bf0ee8b3b2024-08-03T08:50:07ZengFrontiers Media S.A.Frontiers in Systems Biology2674-07022024-02-01410.3389/fsysb.2024.12662791266279Computational inference of chemokine-mediated roles for the vagus nerve in modulating intra- and inter-tissue inflammationAshti M. Shah0Ruben Zamora1Ruben Zamora2Derek Barclay3Jinling Yin4Fayten El-Dehaibi5Meghan Addorisio6Tea Tsaava7Aisling Tynan8Kevin Tracey9Sangeeta S. Chavan10Yoram Vodovotz11Yoram Vodovotz12Department of Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Inflammation and Regeneration Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesInstitute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesInstitute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesInstitute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesInstitute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesInstitute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Inflammation and Regeneration Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesIntroduction: 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.https://www.frontiersin.org/articles/10.3389/fsysb.2024.1266279/fullvagus nervevagotomyinflammationchemokinessystems biology |
| spellingShingle | Ashti M. Shah Ruben Zamora Ruben Zamora Derek Barclay Jinling Yin Fayten El-Dehaibi Meghan Addorisio Tea Tsaava Aisling Tynan Kevin Tracey Sangeeta S. Chavan Yoram Vodovotz Yoram Vodovotz Computational inference of chemokine-mediated roles for the vagus nerve in modulating intra- and inter-tissue inflammation Frontiers in Systems Biology vagus nerve vagotomy inflammation chemokines systems biology |
| title | Computational inference of chemokine-mediated roles for the vagus nerve in modulating intra- and inter-tissue inflammation |
| title_full | Computational inference of chemokine-mediated roles for the vagus nerve in modulating intra- and inter-tissue inflammation |
| title_fullStr | Computational inference of chemokine-mediated roles for the vagus nerve in modulating intra- and inter-tissue inflammation |
| title_full_unstemmed | Computational inference of chemokine-mediated roles for the vagus nerve in modulating intra- and inter-tissue inflammation |
| title_short | Computational inference of chemokine-mediated roles for the vagus nerve in modulating intra- and inter-tissue inflammation |
| title_sort | computational inference of chemokine mediated roles for the vagus nerve in modulating intra and inter tissue inflammation |
| topic | vagus nerve vagotomy inflammation chemokines systems biology |
| url | https://www.frontiersin.org/articles/10.3389/fsysb.2024.1266279/full |
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