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Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s
Group 2 innate lymphoid cells (ILC2s) and type 2 helper T cells (Th2 cells) are the primary source of interleukin 5 (IL-5) and IL-13 during type 2 (allergic) inflammation in the lung. In Th2 cells, T cell receptor (TCR) signaling activates the transcription factors nuclear factor of activated T cell...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206504/ https://www.ncbi.nlm.nih.gov/pubmed/28011865 http://dx.doi.org/10.1084/jem.20161274 |
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author | von Moltke, Jakob O’Leary, Claire E. Barrett, Nora A. Kanaoka, Yoshihide Austen, K. Frank Locksley, Richard M. |
author_facet | von Moltke, Jakob O’Leary, Claire E. Barrett, Nora A. Kanaoka, Yoshihide Austen, K. Frank Locksley, Richard M. |
author_sort | von Moltke, Jakob |
collection | PubMed |
description | Group 2 innate lymphoid cells (ILC2s) and type 2 helper T cells (Th2 cells) are the primary source of interleukin 5 (IL-5) and IL-13 during type 2 (allergic) inflammation in the lung. In Th2 cells, T cell receptor (TCR) signaling activates the transcription factors nuclear factor of activated T cells (NFAT), nuclear factor κB (NF-κB), and activator protein 1 (AP-1) to induce type 2 cytokines. ILC2s lack a TCR and respond instead to locally produced cytokines such as IL-33. Although IL-33 induces AP-1 and NF-κB, NFAT signaling has not been described in ILC2s. In this study, we report a nonredundant NFAT-dependent role for lipid-derived leukotrienes (LTs) in the activation of lung ILC2s. Using cytokine reporter and LT-deficient mice, we find that complete disruption of LT signaling markedly diminishes ILC2 activation and downstream responses during type 2 inflammation. Type 2 responses are equivalently attenuated in IL-33– and LT-deficient mice, and optimal ILC2 activation reflects potent synergy between these pathways. These findings expand our understanding of ILC2 regulation and may have important implications for the treatment of airways disease. |
format | Online Article Text |
id | pubmed-5206504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-52065042017-07-01 Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s von Moltke, Jakob O’Leary, Claire E. Barrett, Nora A. Kanaoka, Yoshihide Austen, K. Frank Locksley, Richard M. J Exp Med Research Articles Group 2 innate lymphoid cells (ILC2s) and type 2 helper T cells (Th2 cells) are the primary source of interleukin 5 (IL-5) and IL-13 during type 2 (allergic) inflammation in the lung. In Th2 cells, T cell receptor (TCR) signaling activates the transcription factors nuclear factor of activated T cells (NFAT), nuclear factor κB (NF-κB), and activator protein 1 (AP-1) to induce type 2 cytokines. ILC2s lack a TCR and respond instead to locally produced cytokines such as IL-33. Although IL-33 induces AP-1 and NF-κB, NFAT signaling has not been described in ILC2s. In this study, we report a nonredundant NFAT-dependent role for lipid-derived leukotrienes (LTs) in the activation of lung ILC2s. Using cytokine reporter and LT-deficient mice, we find that complete disruption of LT signaling markedly diminishes ILC2 activation and downstream responses during type 2 inflammation. Type 2 responses are equivalently attenuated in IL-33– and LT-deficient mice, and optimal ILC2 activation reflects potent synergy between these pathways. These findings expand our understanding of ILC2 regulation and may have important implications for the treatment of airways disease. The Rockefeller University Press 2017-01 /pmc/articles/PMC5206504/ /pubmed/28011865 http://dx.doi.org/10.1084/jem.20161274 Text en © 2017 von Moltke et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles von Moltke, Jakob O’Leary, Claire E. Barrett, Nora A. Kanaoka, Yoshihide Austen, K. Frank Locksley, Richard M. Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s |
title | Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s |
title_full | Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s |
title_fullStr | Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s |
title_full_unstemmed | Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s |
title_short | Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s |
title_sort | leukotrienes provide an nfat-dependent signal that synergizes with il-33 to activate ilc2s |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206504/ https://www.ncbi.nlm.nih.gov/pubmed/28011865 http://dx.doi.org/10.1084/jem.20161274 |
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