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Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms

Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms
Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms
Background

Asthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear.

Objective

We performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients.

Methods

Sixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed.

Results

Significant heterogeneity of T-cell phenotypes was observed, with levels of IL-13–secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and ??-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine–high) and nonatopic forms.

Conclusion

The evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies.
asthma, T lymphocytes, cytokines, mast cells, phenotype, endotype, regulatory T, TH17, TH2, mucosal-associated invariant T-cell
0091-6749
323-333
Hinks, Timothy
c7668ed3-f706-4038-8645-ee6cc6aef29f
Zhou, Xiaoying
84558a96-3129-44de-b295-869d9ee4d19f
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Dimitrov, Borislav D.
366d715f-ffd9-45a1-8415-65de5488472f
Manta, Alexander
2e91eac1-1d67-44ab-b3c1-0b47fa95bf93
Petrossian, Tanya
b52cc87c-f889-4c8b-8d71-7947e58158e9
Lum, Pek Y.
b44892bb-2355-4331-9500-5aa49faad2b0
Smith, Caroline G.
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Ward, Jon A.
a8107b98-069d-4263-bd70-d29d79f07edc
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Walls, Andrew F.
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Gadola, Stephan D.
ef2fa6cf-2ccc-4fea-a7a5-cc03a9d13ab1
Djukanović, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Hinks, Timothy
c7668ed3-f706-4038-8645-ee6cc6aef29f
Zhou, Xiaoying
84558a96-3129-44de-b295-869d9ee4d19f
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Dimitrov, Borislav D.
366d715f-ffd9-45a1-8415-65de5488472f
Manta, Alexander
2e91eac1-1d67-44ab-b3c1-0b47fa95bf93
Petrossian, Tanya
b52cc87c-f889-4c8b-8d71-7947e58158e9
Lum, Pek Y.
b44892bb-2355-4331-9500-5aa49faad2b0
Smith, Caroline G.
0e635f1f-6500-4b52-b111-670f4b0a8deb
Ward, Jon A.
a8107b98-069d-4263-bd70-d29d79f07edc
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Gadola, Stephan D.
ef2fa6cf-2ccc-4fea-a7a5-cc03a9d13ab1
Djukanović, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d

Hinks, Timothy, Zhou, Xiaoying, Staples, Karl J., Dimitrov, Borislav D., Manta, Alexander, Petrossian, Tanya, Lum, Pek Y., Smith, Caroline G., Ward, Jon A., Howarth, Peter H., Walls, Andrew F., Gadola, Stephan D. and Djukanović, Ratko (2015) Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms. Journal of Allergy and Clinical Immunology, 136 (2), 323-333. (doi:10.1016/j.jaci.2015.01.014). (PMID:25746968)

Record type: Article

Abstract

Background

Asthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear.

Objective

We performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients.

Methods

Sixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed.

Results

Significant heterogeneity of T-cell phenotypes was observed, with levels of IL-13–secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and ??-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine–high) and nonatopic forms.

Conclusion

The evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies.

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More information

Accepted/In Press date: 16 January 2015
e-pub ahead of print date: 5 March 2015
Published date: August 2015
Keywords: asthma, T lymphocytes, cytokines, mast cells, phenotype, endotype, regulatory T, TH17, TH2, mucosal-associated invariant T-cell
Organisations: Primary Care & Population Sciences, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 375590
URI: https://eprints.soton.ac.uk/id/eprint/375590
ISSN: 0091-6749
PURE UUID: a58e591b-f2f1-45b6-9f83-a14c7a760171
ORCID for Karl J. Staples: ORCID iD orcid.org/0000-0003-3844-6457
ORCID for Ratko Djukanović: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 30 Mar 2015 11:37
Last modified: 22 Jun 2018 00:37

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Contributors

Author: Timothy Hinks
Author: Xiaoying Zhou
Author: Karl J. Staples ORCID iD
Author: Borislav D. Dimitrov
Author: Alexander Manta
Author: Tanya Petrossian
Author: Pek Y. Lum
Author: Caroline G. Smith
Author: Jon A. Ward
Author: Andrew F. Walls
Author: Stephan D. Gadola

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