Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling.

anaphylaxis basophils cell movement lipid activating nuclear receptors signaling migration neuroinflammatory signaling neutrophils transcriptome analysis

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2022
Historique:
received: 11 08 2022
accepted: 10 11 2022
entrez: 26 12 2022
pubmed: 27 12 2022
medline: 28 12 2022
Statut: epublish

Résumé

Anaphylaxis 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. We sought to identify the global architecture of blood transcriptomic features of anaphylaxis by integrating expression data from human patients and mouse model of anaphylaxis. Bulk RNA-sequencings of peripheral whole blood were performed in: i) 14 emergency department (ED) patients with acute anaphylaxis, predominantly to 1023 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. Our 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.

Sections du résumé

Background
Anaphylaxis 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.
Objective
We sought to identify the global architecture of blood transcriptomic features of anaphylaxis by integrating expression data from human patients and mouse model of anaphylaxis.
Methods
Bulk RNA-sequencings of peripheral whole blood were performed in: i) 14 emergency department (ED) patients with acute anaphylaxis, predominantly to
Results
1023 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.
Conclusion
Our 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.

Identifiants

pubmed: 36569939
doi: 10.3389/fimmu.2022.1016165
pmc: PMC9772259
doi:

Substances chimiques

Allergens 0

Types de publication

Randomized Controlled Trial Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1016165

Subventions

Organisme : Department of Health
Pays : United Kingdom

Informations de copyright

Copyright © 2022 Rijavec, Maver, Turner, Hočevar, Košnik, Yamani, Hogan, Custovic, Peterlin and Korošec.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Matija Rijavec (M)

University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia.
Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.

Aleš Maver (A)

Clinical Institute of Medical Genetics, University Medical Centre, Ljubljana, Slovenia.

Paul J Turner (PJ)

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Keli Hočevar (K)

Clinical Institute of Medical Genetics, University Medical Centre, Ljubljana, Slovenia.

Mitja Košnik (M)

University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia.
Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.

Amnah Yamani (A)

Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States.
Mary H. Weiser Food Allergy Center (MHWFAC), Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States.

Simon P Hogan (SP)

Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States.
Mary H. Weiser Food Allergy Center (MHWFAC), Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States.

Adnan Custovic (A)

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Borut Peterlin (B)

Clinical Institute of Medical Genetics, University Medical Centre, Ljubljana, Slovenia.

Peter Korošec (P)

University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia.
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.

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