Chemokine receptor 4 plays a key role in T cell recruitment into the airways of asthmatic patients
Chemokine receptor 4 plays a key role in T cell recruitment into the airways of asthmatic patients
T lymphocytes of the Th2 type are central orchestrators of airway inflammation in asthma. The mechanisms that regulate their accumulation in the asthmatic airways remains poorly understood. We tested the hypothesis that CCR4, preferentially expressed on T lymphocytes of the Th2 type, plays a critical role in this process. We enumerated by flow cytometry the CCR4-expressing T cells from blood, induced sputum, and biopsy samples of patients with asthma and control subjects. We showed a positive correlation between the numbers of peripheral blood CCR4+ T cells and asthma severity, provided evidence of preferential accumulation of CCR4+ T cells in asthmatic airways, and demonstrated that CCR4+ but not CCR4- cells from patients with asthma produce Th2 cytokines. Explanted airway mucosal biopsy specimens, acquired by bronchoscopy from subjects with asthma, were challenged with allergen and the explant supernatants assayed for T cell chemotactic activity. Allergen-induced ex vivo production of the CCR4 ligand, CCL17 was raised in explants from patients with asthma when compared with healthy controls. Using chemotaxis assays, we showed that the T cell chemotactic activity generated by bronchial explants can be blocked with a selective CCR4 antagonist or by depleting CCR4+ cells from responder cells. These results provide evidence that CCR4 might play a role in allergen-driven Th2 cell accumulation in asthmatic airways. Targeting this chemokine receptor in patients with asthma might reduce Th2 cell-driven airway inflammation; therefore, CCR4 antagonists could be an effective new therapy for asthma. This study also provides wider proof of concept for using tissue explants to study immunomodulatory drugs for asthma.
4568-4574
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
Durkin, Kesta
f57c691d-6653-4e99-8cb2-d28f2cf324aa
Hartmann, Guido
77bc0c76-dc1e-4df7-9ef9-0737bb066f9a
Morjaria, Jaymin
dd29e666-c2db-44f0-99b3-8aefaf420737
Seumois, Gregory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Hall, David
5cf4eeb4-5247-4663-bc36-f7792a6c2c04
Bessant, Christina
61e3922c-360a-4aad-9ee5-9d74402ba22f
Bartholomew, Michelle
8bbfa69a-8e51-42bd-b9ce-e3df08b3f420
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
15 April 2010
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
Durkin, Kesta
f57c691d-6653-4e99-8cb2-d28f2cf324aa
Hartmann, Guido
77bc0c76-dc1e-4df7-9ef9-0737bb066f9a
Morjaria, Jaymin
dd29e666-c2db-44f0-99b3-8aefaf420737
Seumois, Gregory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Hall, David
5cf4eeb4-5247-4663-bc36-f7792a6c2c04
Bessant, Christina
61e3922c-360a-4aad-9ee5-9d74402ba22f
Bartholomew, Michelle
8bbfa69a-8e51-42bd-b9ce-e3df08b3f420
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Vijayanand, Pandurangan, Durkin, Kesta, Hartmann, Guido, Morjaria, Jaymin, Seumois, Gregory, Staples, Karl J., Hall, David, Bessant, Christina, Bartholomew, Michelle, Howarth, Peter H., Friedmann, Peter S. and Djukanovic, Ratko
(2010)
Chemokine receptor 4 plays a key role in T cell recruitment into the airways of asthmatic patients.
Journal of Immunology, 184 (8), .
(doi:10.4049/jimmunol.0901342).
(PMID:20237293)
Abstract
T lymphocytes of the Th2 type are central orchestrators of airway inflammation in asthma. The mechanisms that regulate their accumulation in the asthmatic airways remains poorly understood. We tested the hypothesis that CCR4, preferentially expressed on T lymphocytes of the Th2 type, plays a critical role in this process. We enumerated by flow cytometry the CCR4-expressing T cells from blood, induced sputum, and biopsy samples of patients with asthma and control subjects. We showed a positive correlation between the numbers of peripheral blood CCR4+ T cells and asthma severity, provided evidence of preferential accumulation of CCR4+ T cells in asthmatic airways, and demonstrated that CCR4+ but not CCR4- cells from patients with asthma produce Th2 cytokines. Explanted airway mucosal biopsy specimens, acquired by bronchoscopy from subjects with asthma, were challenged with allergen and the explant supernatants assayed for T cell chemotactic activity. Allergen-induced ex vivo production of the CCR4 ligand, CCL17 was raised in explants from patients with asthma when compared with healthy controls. Using chemotaxis assays, we showed that the T cell chemotactic activity generated by bronchial explants can be blocked with a selective CCR4 antagonist or by depleting CCR4+ cells from responder cells. These results provide evidence that CCR4 might play a role in allergen-driven Th2 cell accumulation in asthmatic airways. Targeting this chemokine receptor in patients with asthma might reduce Th2 cell-driven airway inflammation; therefore, CCR4 antagonists could be an effective new therapy for asthma. This study also provides wider proof of concept for using tissue explants to study immunomodulatory drugs for asthma.
This record has no associated files available for download.
More information
Published date: 15 April 2010
Organisations:
Infection Inflammation & Immunity
Identifiers
Local EPrints ID: 146395
URI: http://eprints.soton.ac.uk/id/eprint/146395
ISSN: 0022-1767
PURE UUID: 0d429ca2-a40f-45a7-a40a-fbad4cf52a6f
Catalogue record
Date deposited: 21 Apr 2010 11:22
Last modified: 14 Mar 2024 02:52
Export record
Altmetrics
Contributors
Author:
Pandurangan Vijayanand
Author:
Kesta Durkin
Author:
Guido Hartmann
Author:
Jaymin Morjaria
Author:
Gregory Seumois
Author:
David Hall
Author:
Christina Bessant
Author:
Michelle Bartholomew
Author:
Peter S. Friedmann
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics