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Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling
ID
Rijavec, Matija
(
Author
),
ID
Maver, Aleš
(
Author
),
ID
Turner, Paul J.
(
Author
),
ID
Hočevar, Keli
(
Author
),
ID
Košnik, Mitja
(
Author
),
ID
Yamani, Amnah
(
Author
),
ID
Hogan, Simon P.
(
Author
),
ID
Custovic, Adnan
(
Author
),
ID
Peterlin, Borut
(
Author
),
ID
Korošec, Peter
(
Author
)
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URL - Source URL, Visit
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1016165/full
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Abstract
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 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. 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.
Language:
English
Keywords:
transcriptome analysis
,
cell movement
,
migration
,
neuroinflammatory signaling
,
lipid activating nuclear receptors signaling
,
anaphylaxis
,
diagnosis
,
mast cells
,
basophils
,
neutrophils
Work type:
Article
Typology:
1.01 - Original Scientific Article
Organization:
BF - Biotechnical Faculty
MF - Faculty of Medicine
FFA - Faculty of Pharmacy
Publication status:
Published
Publication version:
Version of Record
Year:
2022
Number of pages:
15 str.
Numbering:
Vol. 13, art. 1016165
PID:
20.500.12556/RUL-155258
UDC:
575
ISSN on article:
1664-3224
DOI:
10.3389/fimmu.2022.1016165
COBISS.SI-ID:
133240067
Publication date in RUL:
22.03.2024
Views:
352
Downloads:
46
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Record is a part of a journal
Title:
Frontiers in immunology
Shortened title:
Front. immunol.
Publisher:
Frontiers Media
ISSN:
1664-3224
COBISS.SI-ID:
30774233
Licences
License:
CC BY 4.0, Creative Commons Attribution 4.0 International
Link:
http://creativecommons.org/licenses/by/4.0/
Description:
This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Secondary language
Language:
Slovenian
Keywords:
gibanje celic
,
migracija
,
anafilaksija
,
diagnostika
,
mastociti
,
bazofilci
,
nevtrofilci
Projects
Funder:
ARRS - Slovenian Research Agency
Project number:
P3-0360
Name:
Celostna obravnava alergijskih bolezni in astme v Sloveniji: od epidemiologije do genetike
Funder:
Other - Other funder or multiple funders
Funding programme:
NHS Trust, Imperial College Healthcare, NIHR, Biomedical Research Centre
Funder:
Other - Other funder or multiple funders
Funding programme:
Imperial College London
Funder:
NIH - National Institutes of Health
Project number:
AI138177
Funder:
NIH - National Institutes of Health
Project number:
AI112626
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