Imperial College London
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ProfessorStephenDurham

Faculty of Medicine, National Heart & Lung Institute

Professor of Allergy and Respiratory
 
 
 
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Contact

 

+44 (0)20 7351 8024s.durham

 
 
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Location

 

Fulham RoadRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sharif:2021:10.1016/j.jaci.2020.10.035,
author = {Sharif, H and Acharya, S and Dhondalay, GKR and Varricchi, G and Krasner-Macleod, S and Laisuan, W and Switzer, A and Lenormand, M and Kashe, E and Parkin, RV and Yi, Y and Koc, M and Fedina, O and Vilà-Nadal, G and Marone, G and Eifan, A and Scadding, GW and Fear, DJ and Nadeau, KC and Durham, SR and Shamji, MH},
doi = {10.1016/j.jaci.2020.10.035},
journal = {Journal of Allergy and Clinical Immunology},
pages = {663--676},
title = {Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy},
url = {http://dx.doi.org/10.1016/j.jaci.2020.10.035},
volume = {147},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Allergen-specific immunotherapy (AIT) is a disease-modifying treatment that induces long-term T cell tolerance. OBJECTIVE: To evaluate the role of circulating CXCR5+PD-1+T follicular helper (cTFH) and T follicular regulatory (TFR) cells following grass pollen subcutaneous (SCIT) and sublingual (SLIT) immunotherapy and the accompanying changes in their chromatin landscape. METHODS: Phenotype and function of cTFH cells were initially evaluated in grass pollen-allergics (GPA, n= 28) and non-atopic controls (NAC, n=13) by mathematical algorithms developed to manage high-dimensional data and cell culture, respectively. cTFH and TFR cells were further enumerated in NAC (n=12), GPA (n=14), SCIT (n=10) and SLIT (n=8)-treated groups. Chromatin accessibility in cTFH and TFR cells was assessed by ATAC-seq to investigate epigenetic mechanisms underlying the differences between NAC, GPA, SCIT and SLIT. RESULTS: cTFH cells were shown to be distinct from TH2 and TH2A cell subsets, capable of secreting IL-4 and IL-21. Both cytokines synergistically promoted B cell class switching to IgE and plasma cell differentiation. Grass pollen allergen induced cTFH cell proliferation in GPA but not in NAC (P<.05). cTFH cells were higher in GPA compared to NAC and were lower in SCIT and SLIT (P<.01). Time-dependent induction of IL-4, IL-21 and IL-6 were observed in nasal mucosa following intranasal allergen challenge in GPA but not in SCIT and SLIT groups. TFR and IL-10+ cTFH cells were induced in SCIT and SLIT (all, P<.01). ATAC-seq analyses revealed differentially accessible chromatin regions in all groups. CONCLUSION: For the first time, we showed dysregulation of cTFH cells in GPA compared to NAC, SCIT and SLIT and induction of TFR and IL-10+ cTFH cells following SCIT and SLIT. Changes in the chromatin landscape were observed following AIT in cTFH and TFR cells.
AU  - Sharif,H
AU  - Acharya,S
AU  - Dhondalay,GKR
AU  - Varricchi,G
AU  - Krasner-Macleod,S
AU  - Laisuan,W
AU  - Switzer,A
AU  - Lenormand,M
AU  - Kashe,E
AU  - Parkin,RV
AU  - Yi,Y
AU  - Koc,M
AU  - Fedina,O
AU  - Vilà-Nadal,G
AU  - Marone,G
AU  - Eifan,A
AU  - Scadding,GW
AU  - Fear,DJ
AU  - Nadeau,KC
AU  - Durham,SR
AU  - Shamji,MH
DO  - 10.1016/j.jaci.2020.10.035
EP  - 676
PY  - 2021///
SN  - 0091-6749
SP  - 663
TI  - Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2020.10.035
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33160969
UR  - https://www.sciencedirect.com/science/article/pii/S009167492031561X?via%3Dihub
UR  - http://hdl.handle.net/10044/1/85113
VL  - 147
ER  -
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