Imperial College London
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MissSimoneWalker

Faculty of Medicine, National Heart & Lung Institute

Senior Research Technician
 
 
 
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s.walker

 
 
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Location

 

Desk 28Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Branchett:2021:10.1016/j.jaci.2021.01.026,
author = {Branchett, WJ and Cook, J and Oliver, RA and Bruno, N and Walker, SA and Stlting, H and Mack, M and OGarra, A and Saglani, S and Lloyd, CM},
doi = {10.1016/j.jaci.2021.01.026},
journal = {Journal of Allergy and Clinical Immunology},
pages = {1892--1906},
title = {Airway macrophage-intrinsic TGF-β1 regulates pulmonary immunity during early life allergen exposure},
url = {http://dx.doi.org/10.1016/j.jaci.2021.01.026},
volume = {147},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundEarly life represents a major risk window for asthma development. However, the mechanisms controlling the threshold for establishment of allergic airway inflammation in early life are incompletely understood. Airway macrophages (AMs) regulate pulmonary allergic responses and undergo TGF-β–dependent postnatal development, but the role of AM maturation factors such as TGF-β in controlling the threshold for pathogenic immune responses to inhaled allergens remains unclear.ObjectiveOur aim was to test the hypothesis that AM-derived TGF-β1 regulates pathogenic immunity to inhaled allergen in early life.MethodsConditional knockout (Tgfb1ΔCD11c) mice, with TGF-β1 deficiency in AMs and other CD11c+ cells, were analyzed throughout early life and following neonatal house dust mite (HDM) inhalation. The roles of specific chemokine receptors were determined by using in vivo blocking antibodies.ResultsAM-intrinsic TGF-β1 was redundant for initial population of the neonatal lung with AMs, but AMs from Tgfb1ΔCD11c mice failed to adopt a mature homeostatic AM phenotype in the first weeks of life. Evidence of constitutive TGF-β1 signaling was also observed in pediatric human AMs. TGF-β1–deficient AMs expressed enhanced levels of monocyte-attractant chemokines, and accordingly, Tgfb1ΔCD11c mice exposed to HDM throughout early life accumulated CCR2-dependent inflammatory CD11c+ mononuclear phagocytes into the airway niche that expressed the proallergic chemokine CCL8. Tgfb1ΔCD11c mice displayed augmented TH2, group 2 innate lymphoid cell, and airway remodeling responses to HDM, which were ameliorated by blockade of the CCL8 receptor CCR8.ConclusionOur results highlight a causal relationship between AM maturity, chemokines, and pathogenic immunity to environmental stimuli in early life and identify TGF-β1 as a key regulator of this.
AU  - Branchett,WJ
AU  - Cook,J
AU  - Oliver,RA
AU  - Bruno,N
AU  - Walker,SA
AU  - Stlting,H
AU  - Mack,M
AU  - OGarra,A
AU  - Saglani,S
AU  - Lloyd,CM
DO  - 10.1016/j.jaci.2021.01.026
EP  - 1906
PY  - 2021///
SN  - 0091-6749
SP  - 1892
TI  - Airway macrophage-intrinsic TGF-β1 regulates pulmonary immunity during early life allergen exposure
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2021.01.026
UR  - https://www.sciencedirect.com/science/article/pii/S0091674921001731?via%3Dihub
UR  - http://hdl.handle.net/10044/1/86945
VL  - 147
ER  -
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