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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...

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Autores principales: von Moltke, Jakob, O’Leary, Claire E., Barrett, Nora A., Kanaoka, Yoshihide, Austen, K. Frank, Locksley, Richard M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
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.
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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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