| Title: |
Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy |
| Authors: |
Sharif, H; Acharya, S; Dhondalay, GKR; Varricchi, G; Krasner-Macleod, S; Laisuan, W; Switzer, A; Lenormand, M; Kashe, E; Parkin, RV; Yi, Y; Koc, M; Fedina, O; Vilà-Nadal, G; Marone, G; Eifan, A; Scadding, GW; Fear, DJ; Nadeau, KC; Durham, SR; Shamji, MH |
| Source: |
676 ; 663 |
| Publisher Information: |
Elsevier |
| Publication Year: |
2020 |
| Collection: |
Imperial College London: Spiral |
| Subject Terms: |
ATAC-seq; Allergy; T follicular helper cells; T follicular regulatory cells; allergen-specific immunotherapy; chromatin accessibility; seasonal allergic rhinitis; 1107 Immunology |
| Subject Geographic: |
United States |
| Description: |
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 |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Journal of Allergy and Clinical Immunology; http://hdl.handle.net/10044/1/85113 |
| DOI: |
10.1016/j.jaci.2020.10.035 |
| Availability: |
http://hdl.handle.net/10044/1/85113; https://doi.org/10.1016/j.jaci.2020.10.035 |
| Rights: |
© 2020 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This pre-proof version is available open access under a CC-BY-NC-ND License (https://creativecommons.org/licenses/by-nc-nd/4.0/) ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.9FEEF749 |
| Database: |
BASE |