Eosinophils and pleural macrophages counter regulate IL-33-elicited airway inflammation via the 12/15-lipoxygenase pathway

IntroductionFatty acid metabolism plays a crucial role in regulating airway inflammation through the synthesis of lipid mediators. We have previously demonstrated that a 12/15-lipoxygenase (12/15-LOX or Alox15)-derived mediator attenuates IL-33-induced eosinophilic airway inflammation in mice. Howev...

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Main Authors: Emi Ito, Reika Hayashizaki, Takuro Hosaka, Tsuyoshi Yamane, Jun Miyata, Yosuke Isobe, Makoto Arita
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1565670/full
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author Emi Ito
Emi Ito
Reika Hayashizaki
Reika Hayashizaki
Takuro Hosaka
Takuro Hosaka
Tsuyoshi Yamane
Jun Miyata
Jun Miyata
Yosuke Isobe
Yosuke Isobe
Yosuke Isobe
Makoto Arita
Makoto Arita
Makoto Arita
author_facet Emi Ito
Emi Ito
Reika Hayashizaki
Reika Hayashizaki
Takuro Hosaka
Takuro Hosaka
Tsuyoshi Yamane
Jun Miyata
Jun Miyata
Yosuke Isobe
Yosuke Isobe
Yosuke Isobe
Makoto Arita
Makoto Arita
Makoto Arita
author_sort Emi Ito
collection DOAJ
description IntroductionFatty acid metabolism plays a crucial role in regulating airway inflammation through the synthesis of lipid mediators. We have previously demonstrated that a 12/15-lipoxygenase (12/15-LOX or Alox15)-derived mediator attenuates IL-33-induced eosinophilic airway inflammation in mice. However, the cellular sources of these mediators remain unclear.MethodsTo identify the cellular sources, we used several cell type-specific conditional 12/15-LOX-deficient mice.ResultsWe found that eosinophils and pleural macrophages were the major 12/15-LOX-expressing cell types responsible for attenuating airway inflammation. Eosinophils were the major population of 12/15-LOX-expressing cells found in inflamed lung tissue. In addition, pleural macrophages were the major population of 12/15-LOX-expressing cells in the thoracic cavity and were found to translocate into inflamed lung tissue in response to airway inflammation.DiscussionThis study suggests that eosinophils and pleural macrophages cooperatively regulate eosinophilic airway inflammation via 12/15-LOX expression. Targeting 12/15-LOX metabolism in these cells may offer new therapeutic strategies for severe asthma.
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publishDate 2025-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-0ee28fef99f0410b98d7f7af2a9711912025-08-20T03:10:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15656701565670Eosinophils and pleural macrophages counter regulate IL-33-elicited airway inflammation via the 12/15-lipoxygenase pathwayEmi Ito0Emi Ito1Reika Hayashizaki2Reika Hayashizaki3Takuro Hosaka4Takuro Hosaka5Tsuyoshi Yamane6Jun Miyata7Jun Miyata8Yosuke Isobe9Yosuke Isobe10Yosuke Isobe11Makoto Arita12Makoto Arita13Makoto Arita14Division of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy, Tokyo, JapanLaboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, JapanDivision of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy, Tokyo, JapanLaboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, JapanDivision of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy, Tokyo, JapanLaboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, JapanLaboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, JapanLaboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, JapanDivision of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, JapanDivision of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy, Tokyo, JapanLaboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, JapanCellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, JapanDivision of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy, Tokyo, JapanLaboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, JapanCellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, JapanIntroductionFatty acid metabolism plays a crucial role in regulating airway inflammation through the synthesis of lipid mediators. We have previously demonstrated that a 12/15-lipoxygenase (12/15-LOX or Alox15)-derived mediator attenuates IL-33-induced eosinophilic airway inflammation in mice. However, the cellular sources of these mediators remain unclear.MethodsTo identify the cellular sources, we used several cell type-specific conditional 12/15-LOX-deficient mice.ResultsWe found that eosinophils and pleural macrophages were the major 12/15-LOX-expressing cell types responsible for attenuating airway inflammation. Eosinophils were the major population of 12/15-LOX-expressing cells found in inflamed lung tissue. In addition, pleural macrophages were the major population of 12/15-LOX-expressing cells in the thoracic cavity and were found to translocate into inflamed lung tissue in response to airway inflammation.DiscussionThis study suggests that eosinophils and pleural macrophages cooperatively regulate eosinophilic airway inflammation via 12/15-LOX expression. Targeting 12/15-LOX metabolism in these cells may offer new therapeutic strategies for severe asthma.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1565670/fulleosinophilspleural macrophages12/15-lipoxygenaseIL-33lipidomics
spellingShingle Emi Ito
Emi Ito
Reika Hayashizaki
Reika Hayashizaki
Takuro Hosaka
Takuro Hosaka
Tsuyoshi Yamane
Jun Miyata
Jun Miyata
Yosuke Isobe
Yosuke Isobe
Yosuke Isobe
Makoto Arita
Makoto Arita
Makoto Arita
Eosinophils and pleural macrophages counter regulate IL-33-elicited airway inflammation via the 12/15-lipoxygenase pathway
Frontiers in Immunology
eosinophils
pleural macrophages
12/15-lipoxygenase
IL-33
lipidomics
title Eosinophils and pleural macrophages counter regulate IL-33-elicited airway inflammation via the 12/15-lipoxygenase pathway
title_full Eosinophils and pleural macrophages counter regulate IL-33-elicited airway inflammation via the 12/15-lipoxygenase pathway
title_fullStr Eosinophils and pleural macrophages counter regulate IL-33-elicited airway inflammation via the 12/15-lipoxygenase pathway
title_full_unstemmed Eosinophils and pleural macrophages counter regulate IL-33-elicited airway inflammation via the 12/15-lipoxygenase pathway
title_short Eosinophils and pleural macrophages counter regulate IL-33-elicited airway inflammation via the 12/15-lipoxygenase pathway
title_sort eosinophils and pleural macrophages counter regulate il 33 elicited airway inflammation via the 12 15 lipoxygenase pathway
topic eosinophils
pleural macrophages
12/15-lipoxygenase
IL-33
lipidomics
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1565670/full
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