Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling
BackgroundAnaphylaxis is an acute life-threatening allergic reaction and a concern at a global level; therefore, further progress in understanding the underlying mechanisms and more effective strategies for diagnosis, prevention and management are needed.ObjectiveWe sought to identify the global arc...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1016165/full |
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| author | Matija Rijavec Matija Rijavec Aleš Maver Paul J. Turner Keli Hočevar Mitja Košnik Mitja Košnik Amnah Yamani Amnah Yamani Simon P. Hogan Simon P. Hogan Adnan Custovic Borut Peterlin Peter Korošec Peter Korošec |
| author_facet | Matija Rijavec Matija Rijavec Aleš Maver Paul J. Turner Keli Hočevar Mitja Košnik Mitja Košnik Amnah Yamani Amnah Yamani Simon P. Hogan Simon P. Hogan Adnan Custovic Borut Peterlin Peter Korošec Peter Korošec |
| author_sort | Matija Rijavec |
| collection | DOAJ |
| description | BackgroundAnaphylaxis is an acute life-threatening allergic reaction and a concern at a global level; therefore, further progress in understanding the underlying mechanisms and more effective strategies for diagnosis, prevention and management are needed.ObjectiveWe sought to identify the global architecture of blood transcriptomic features of anaphylaxis by integrating expression data from human patients and mouse model of anaphylaxis.MethodsBulk RNA-sequencings of peripheral whole blood were performed in: i) 14 emergency department (ED) patients with acute anaphylaxis, predominantly to Hymenoptera venom, ii) 11 patients with peanut allergy undergoing double-blind, placebo-controlled food challenge (DBPCFC) to peanut, iii) murine model of IgE-mediated anaphylaxis. Integrative characterisation of differential gene expression, immune cell-type-specific gene expression profiles, and functional and pathway analysis was undertaken.Results1023 genes were commonly and significantly dysregulated during anaphylaxis in ED and DBPCFC patients; of those genes, 29 were also dysregulated in the mouse model. Cell-type-specific gene expression profiles showed a rapid downregulation of blood basophil and upregulation of neutrophil signature in ED and DBPCFC patients and the mouse model, but no consistent and/or significant differences were found for other blood cells. Functional and pathway analysis demonstrated that human and mouse blood transcriptomic signatures of anaphylaxis follow trajectories of upregulation of cell movement, migration and neuroinflammatory signalling, and downregulation of lipid activating nuclear receptors signalling.ConclusionOur study highlights the matched and extensive blood transcriptomic changes and suggests the involvement of discrete cellular components and upregulation of migration and neuroinflammatory pathways during anaphylaxis. |
| first_indexed | 2024-04-11T13:33:47Z |
| format | Article |
| id | doaj.art-e91dde97664e446caf70faaa396cf91c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T13:33:47Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e91dde97664e446caf70faaa396cf91c2022-12-22T04:21:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10161651016165Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signallingMatija Rijavec0Matija Rijavec1Aleš Maver2Paul J. Turner3Keli Hočevar4Mitja Košnik5Mitja Košnik6Amnah Yamani7Amnah Yamani8Simon P. Hogan9Simon P. Hogan10Adnan Custovic11Borut Peterlin12Peter Korošec13Peter Korošec14University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, SloveniaBiotechnical Faculty, University of Ljubljana, Ljubljana, SloveniaClinical Institute of Medical Genetics, University Medical Centre, Ljubljana, SloveniaNational Heart and Lung Institute, Imperial College London, London, United KingdomClinical Institute of Medical Genetics, University Medical Centre, Ljubljana, SloveniaUniversity Clinic of Respiratory and Allergic Diseases Golnik, Golnik, SloveniaMedical Faculty, University of Ljubljana, Ljubljana, SloveniaDepartment of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, United StatesMary H. Weiser Food Allergy Center (MHWFAC), Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, United StatesDepartment of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, United StatesMary H. Weiser Food Allergy Center (MHWFAC), Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, United StatesNational Heart and Lung Institute, Imperial College London, London, United KingdomClinical Institute of Medical Genetics, University Medical Centre, Ljubljana, SloveniaUniversity Clinic of Respiratory and Allergic Diseases Golnik, Golnik, SloveniaFaculty of Pharmacy, University of Ljubljana, Ljubljana, SloveniaBackgroundAnaphylaxis is an acute life-threatening allergic reaction and a concern at a global level; therefore, further progress in understanding the underlying mechanisms and more effective strategies for diagnosis, prevention and management are needed.ObjectiveWe sought to identify the global architecture of blood transcriptomic features of anaphylaxis by integrating expression data from human patients and mouse model of anaphylaxis.MethodsBulk RNA-sequencings of peripheral whole blood were performed in: i) 14 emergency department (ED) patients with acute anaphylaxis, predominantly to Hymenoptera venom, ii) 11 patients with peanut allergy undergoing double-blind, placebo-controlled food challenge (DBPCFC) to peanut, iii) murine model of IgE-mediated anaphylaxis. Integrative characterisation of differential gene expression, immune cell-type-specific gene expression profiles, and functional and pathway analysis was undertaken.Results1023 genes were commonly and significantly dysregulated during anaphylaxis in ED and DBPCFC patients; of those genes, 29 were also dysregulated in the mouse model. Cell-type-specific gene expression profiles showed a rapid downregulation of blood basophil and upregulation of neutrophil signature in ED and DBPCFC patients and the mouse model, but no consistent and/or significant differences were found for other blood cells. Functional and pathway analysis demonstrated that human and mouse blood transcriptomic signatures of anaphylaxis follow trajectories of upregulation of cell movement, migration and neuroinflammatory signalling, and downregulation of lipid activating nuclear receptors signalling.ConclusionOur study highlights the matched and extensive blood transcriptomic changes and suggests the involvement of discrete cellular components and upregulation of migration and neuroinflammatory pathways during anaphylaxis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1016165/fulltranscriptome analysisanaphylaxisbasophilsneutrophilscell movementmigration |
| spellingShingle | Matija Rijavec Matija Rijavec Aleš Maver Paul J. Turner Keli Hočevar Mitja Košnik Mitja Košnik Amnah Yamani Amnah Yamani Simon P. Hogan Simon P. Hogan Adnan Custovic Borut Peterlin Peter Korošec Peter Korošec Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling Frontiers in Immunology transcriptome analysis anaphylaxis basophils neutrophils cell movement migration |
| title | Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling |
| title_full | Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling |
| title_fullStr | Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling |
| title_full_unstemmed | Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling |
| title_short | Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling |
| title_sort | integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement migration and neuroinflammatory signalling |
| topic | transcriptome analysis anaphylaxis basophils neutrophils cell movement migration |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1016165/full |
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