Imperial College London
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Professor Reiko J. Tanaka

Faculty of Engineering, Department of Bioengineering

Professor of Computational Systems Biology & Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6374r.tanaka Website

 
 
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Location

 

RSM 3.10Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tian:2024:10.1111/cea.14425,
author = {Tian, K and Dangarh, P and Zhang, H and Hines, CL and Bush, A and Pybus, HJ and Harker, JA and Lloyd, CM and Tanaka, RJ and Saglani, S},
doi = {10.1111/cea.14425},
journal = {Clin Exp Allergy},
pages = {109--119},
title = {Role of epithelial barrier function in inducing type 2 immunity following early-life viral infection.},
url = {http://dx.doi.org/10.1111/cea.14425},
volume = {54},
year = {2024}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Preschool wheeze attacks triggered by recurrent viral infections, including respiratory syncytial virus (RSV), are associated with an increased risk of childhood asthma. However, mechanisms that lead to asthma following early-life viral wheezing remain uncertain. METHODS: To investigate a causal relationship between early-life RSV infections and onset of type 2 immunity, we developed a neonatal murine model of recurrent RSV infection, in vivo and in silico, and evaluated the dynamical changes of altered airway barrier function and downstream immune responses, including eosinophilia, mucus secretion and type 2 immunity. RESULTS: RSV infection of neonatal BALB/c mice at 5 and 15 days of age induced robust airway eosinophilia, increased pulmonary CD4+ IL-13+ and CD4+ IL-5+ cells, elevated levels of IL-13 and IL-5 and increased airway mucus at 20 days of age. Increased bronchoalveolar lavage albumin levels, suggesting epithelial barrier damage, were present and persisted following the second RSV infection. Computational in silico simulations demonstrated that recurrent RSV infection resulted in severe damage of the airway barrier (epithelium), triggering the onset of type 2 immunity. The in silico results also demonstrated that recurrent infection is not always necessary for the development of type 2 immunity, which could also be triggered with single infection of high viral load or when the epithelial barrier repair is compromised. CONCLUSIONS: The neonatal murine model demonstrated that recurrent RSV infection in early life alters airway barrier function and promotes type 2 immunity. A causal relationship between airway barrier function and type 2 immunity was suggested using in silico model simulations.
AU  - Tian,K
AU  - Dangarh,P
AU  - Zhang,H
AU  - Hines,CL
AU  - Bush,A
AU  - Pybus,HJ
AU  - Harker,JA
AU  - Lloyd,CM
AU  - Tanaka,RJ
AU  - Saglani,S
DO  - 10.1111/cea.14425
EP  - 119
PY  - 2024///
SP  - 109
TI  - Role of epithelial barrier function in inducing type 2 immunity following early-life viral infection.
T2  - Clin Exp Allergy
UR  - http://dx.doi.org/10.1111/cea.14425
UR  - https://www.ncbi.nlm.nih.gov/pubmed/38011856
VL  - 54
ER  -
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