A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality

Mucosal tissues contain large numbers of memory CD4+ T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4+ T cells at barrier s...

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Main Authors: Holmkvist, P., Roepstorff, K., Uronen-Hansson, H., Sandén, C., Gudjonsson, S., Patschan, O., Grip, O., Marsal, J., Schmidtchen, A., Hornum, L., Erjefält, J. S., Håkansson, K., Agace, W W.
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2015
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Online Access:https://hdl.handle.net/10356/103806
http://hdl.handle.net/10220/24590
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1038062022-02-16T16:27:50Z A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality Holmkvist, P. Roepstorff, K. Uronen-Hansson, H. Sandén, C. Gudjonsson, S. Patschan, O. Grip, O. Marsal, J. Schmidtchen, A. Hornum, L. Erjefält, J. S. Håkansson, K. Agace, W W. Lee Kong Chian School of Medicine (LKCMedicine) DRNTU::Science::Biological sciences::Microbiology::Immunology Mucosal tissues contain large numbers of memory CD4+ T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4+ T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα+DR3+CD4+ T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte–macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα+DR3+CD4+ T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα+DR3+ CD4+ T cells may contribute to antigen-independent innate responses at barrier surfaces. Published version 2015-01-12T06:24:05Z 2019-12-06T21:20:43Z 2015-01-12T06:24:05Z 2019-12-06T21:20:43Z 2014 2014 Journal Article Holmkvist, P., Roepstorff, K., Uronen-Hansson, H., Sandén, C., Gudjonsson, S., Patschan, O., et al. (2014). A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality. Mucosal immunology, 8, 545-558 1933-0219 https://hdl.handle.net/10356/103806 http://hdl.handle.net/10220/24590 10.1038/mi.2014.87 25269704 en Mucosal immunology © 2014 Society for Mucosal Immunology. This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/. 14 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences::Microbiology::Immunology
spellingShingle DRNTU::Science::Biological sciences::Microbiology::Immunology
Holmkvist, P.
Roepstorff, K.
Uronen-Hansson, H.
Sandén, C.
Gudjonsson, S.
Patschan, O.
Grip, O.
Marsal, J.
Schmidtchen, A.
Hornum, L.
Erjefält, J. S.
Håkansson, K.
Agace, W W.
A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality
description Mucosal tissues contain large numbers of memory CD4+ T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4+ T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα+DR3+CD4+ T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte–macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα+DR3+CD4+ T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα+DR3+ CD4+ T cells may contribute to antigen-independent innate responses at barrier surfaces.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Holmkvist, P.
Roepstorff, K.
Uronen-Hansson, H.
Sandén, C.
Gudjonsson, S.
Patschan, O.
Grip, O.
Marsal, J.
Schmidtchen, A.
Hornum, L.
Erjefält, J. S.
Håkansson, K.
Agace, W W.
format Article
author Holmkvist, P.
Roepstorff, K.
Uronen-Hansson, H.
Sandén, C.
Gudjonsson, S.
Patschan, O.
Grip, O.
Marsal, J.
Schmidtchen, A.
Hornum, L.
Erjefält, J. S.
Håkansson, K.
Agace, W W.
author_sort Holmkvist, P.
title A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality
title_short A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality
title_full A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality
title_fullStr A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality
title_full_unstemmed A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality
title_sort major population of mucosal memory cd4+ t cells, coexpressing il-18rα and dr3, display innate lymphocyte functionality
publishDate 2015
url https://hdl.handle.net/10356/103806
http://hdl.handle.net/10220/24590
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