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Synergistic activation of pro-inflammatory type-2 CD8+ T lymphocytes by lipid mediators in severe eosinophilic asthma

Synergistic activation of pro-inflammatory type-2 CD8+ T lymphocytes by lipid mediators in severe eosinophilic asthma
Synergistic activation of pro-inflammatory type-2 CD8+ T lymphocytes by lipid mediators in severe eosinophilic asthma

Human type-2 CD8+ T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia—a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+CRTH2+ (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2 (PGD2) and cysteinyl leukotriene E4 (LTE4) are also increased in the airways of the same group of patients. In vitro PGD2 and LTE4 function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines, which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.

1933-0219
1-12
Hilvering, Bart
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Hinks, Timothy S.C.
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Stöger, Linda
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Marchi, Emanuele
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Salimi, Maryam
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Shrimanker, Rahul
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Liu, Wei
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Chen, Wentao
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Luo, Jian
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Go, Simei
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Powell, Timothy
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Cane, Jennifer
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Thulborn, Samantha
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Kurioka, Ayako
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Leng, Tianqi
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Matthews, Jamie
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Connolly, Clare
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Borg, Catherine
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Bafadhel, Mona
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Willberg, Christian B.
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Ramasamy, Adaikalavan
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Djukanović, Ratko
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Ogg, Graham
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Pavord, Ian D.
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Klenerman, Paul
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Xue, Luzheng
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Hilvering, Bart
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Hinks, Timothy S.C.
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Stöger, Linda
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Marchi, Emanuele
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Salimi, Maryam
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Shrimanker, Rahul
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Liu, Wei
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Chen, Wentao
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Luo, Jian
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Go, Simei
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Powell, Timothy
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Cane, Jennifer
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Thulborn, Samantha
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Kurioka, Ayako
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Leng, Tianqi
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Matthews, Jamie
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Connolly, Clare
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Borg, Catherine
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Bafadhel, Mona
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Willberg, Christian B.
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Ramasamy, Adaikalavan
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Djukanović, Ratko
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Ogg, Graham
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Pavord, Ian D.
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Klenerman, Paul
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Xue, Luzheng
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Hilvering, Bart, Hinks, Timothy S.C., Stöger, Linda, Marchi, Emanuele, Salimi, Maryam, Shrimanker, Rahul, Liu, Wei, Chen, Wentao, Luo, Jian, Go, Simei, Powell, Timothy, Cane, Jennifer, Thulborn, Samantha, Kurioka, Ayako, Leng, Tianqi, Matthews, Jamie, Connolly, Clare, Borg, Catherine, Bafadhel, Mona, Willberg, Christian B., Ramasamy, Adaikalavan, Djukanović, Ratko, Ogg, Graham, Pavord, Ian D., Klenerman, Paul and Xue, Luzheng (2018) Synergistic activation of pro-inflammatory type-2 CD8+ T lymphocytes by lipid mediators in severe eosinophilic asthma. Mucosal Immunology, 1-12. (doi:10.1038/s41385-018-0049-9).

Record type: Article

Abstract

Human type-2 CD8+ T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia—a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+CRTH2+ (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2 (PGD2) and cysteinyl leukotriene E4 (LTE4) are also increased in the airways of the same group of patients. In vitro PGD2 and LTE4 function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines, which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.

Full text not available from this repository.

More information

Accepted/In Press date: 15 June 2018
e-pub ahead of print date: 15 June 2018

Identifiers

Local EPrints ID: 421830
URI: https://eprints.soton.ac.uk/id/eprint/421830
ISSN: 1933-0219
PURE UUID: 2e201f0f-82f6-42bd-9112-5ce99481a99d
ORCID for Ratko Djukanović: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 29 Jun 2018 16:30
Last modified: 14 Mar 2019 01:55

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Contributors

Author: Bart Hilvering
Author: Linda Stöger
Author: Emanuele Marchi
Author: Maryam Salimi
Author: Rahul Shrimanker
Author: Wei Liu
Author: Wentao Chen
Author: Jian Luo
Author: Simei Go
Author: Timothy Powell
Author: Jennifer Cane
Author: Samantha Thulborn
Author: Ayako Kurioka
Author: Tianqi Leng
Author: Jamie Matthews
Author: Clare Connolly
Author: Catherine Borg
Author: Mona Bafadhel
Author: Christian B. Willberg
Author: Adaikalavan Ramasamy
Author: Graham Ogg
Author: Ian D. Pavord
Author: Paul Klenerman
Author: Luzheng Xue

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