Dysregulated fatty acid metabolism in nasal polyp‐derived eosinophils from patients with chronic rhinosinusitis

Miyata, Jun; Fukunaga, Koichi; Kawashima, Yusuke; Watanabe, Takashi; Saitoh, Akina; Hirosaki, Tomomi; Araki, Yasutomo; Kikawada, Toru; Betsuyaku, Tomoko; Ohara, Osamu; Arita, Makoto

doi:10.1111/all.13726

Cited by 64 publications

(45 citation statements)

References 45 publications

(54 reference statements)

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“…Moreover, recent studies have revealed that eosinophils participate in the lipid network for the production of anti-inflammatory and/or pro-resolution lipid mediators [49][50][51]. It is also indicated that eosinophils may be involved in the control of nasal allergy, but details on the mechanisms have been unclear [52]. In the present study, we demonstrated the novel function of eosinophils in the control of allergic responses.…”

Section: Discussionsupporting

confidence: 51%

Dietary Omega-3 Fatty Acid Dampens Allergic Rhinitis via Eosinophilic Production of the Anti-Allergic Lipid Mediator 15-Hydroxyeicosapentaenoic Acid in Mice

et al. 2019

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The metabolism and generation of bioactive lipid mediators are key events in the exertion of the beneficial effects of dietary omega-3 fatty acids in the regulation of allergic inflammation. Here, we found that dietary linseed oil, which contains high amounts of alpha-linolenic acid (ALA) dampened allergic rhinitis through eosinophilic production of 15-hydroxyeicosapentaenoic acid (15-HEPE), a metabolite of eicosapentaenoic acid (EPA). Lipidomic analysis revealed that 15-HEPE was particularly accumulated in the nasal passage of linseed oil-fed mice after the development of allergic rhinitis with the increasing number of eosinophils. Indeed, the conversion of EPA to 15-HEPE was mediated by the 15-lipoxygenase activity of eosinophils. Intranasal injection of 15-HEPE dampened allergic symptoms by inhibiting mast cell degranulation, which was mediated by the action of peroxisome proliferator-activated receptor gamma. These findings identify 15-HEPE as a novel EPA-derived, and eosinophil-dependent anti-allergic metabolite, and provide a preventive and therapeutic strategy against allergic rhinitis.

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Section: Discussionsupporting

confidence: 51%

Dietary Omega-3 Fatty Acid Dampens Allergic Rhinitis via Eosinophilic Production of the Anti-Allergic Lipid Mediator 15-Hydroxyeicosapentaenoic Acid in Mice

et al. 2019

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“…For instance, alveolar macrophages isolated from severe asthma patients show reduced LXA 4 and increased LTB 4 production 59 . Furthermore, eosinophils derived from chronic rhinosinusitis patients had a reduced biosynthesis of 12/15‐LOX‐derived mediators 60 . Finally, eosinophils derived from severe asthma patients showed a reduction in PD1 biosynthesis 61 .…”

Section: Discussionmentioning

confidence: 99%

Sex‐mediated elevation of the specialized pro‐resolving lipid mediator levels in a Sjögren's syndrome mouse model

Parashar

Schulte²,

Hardt

et al. 2020

FASEB j.

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Our previous results showed that the specialized pro‐resolving mediator (SPM) Resolvin D1 (RvD1) promotes resolution of inflammation in salivary glands in non‐obese diabetic (NOD)/ShiLtJ, a mouse model for Sjögren's syndrome (SS). Additionally, mice lacking the RvD1 receptor ALX/FPR2 show defective innate and adaptive immune responses in salivary glands. Particularly, ALX/FPR2 KO mice exhibit exacerbated inflammation in their salivary glands in response to systemic LPS treatment. Moreover, female ALX/FPR2 KO mice show increased autoantibody production and loss of salivary gland function with age. Together, these studies suggest that an underlying SPM dysregulation could be contributing to SS progression. Therefore, we investigated whether SPM production is altered in NOD/ShiLtJ using metabololipidomics and enzyme‐linked immunosorbent assay (ELISA). Our results demonstrate that SPM levels were broadly elevated in plasma collected from NOD/ShiLtJ female mice after disease onset, whereas these drastic changes did not occur in male mice. Moreover, gene expression of enzymes involved in SPM biosynthesis were altered in submandibular glands (SMG) from NOD/ShiLtJ female mice after disease onset, with 5‐LOX and 12/15‐LOX being downregulated and upregulated, respectively. Despite this dysregulation, the abundances of the SPM products of these enzymes (ie, RvD1 and RvD2) were unaltered in freshly isolated SMG cells suggesting that other cell populations (eg, lymphocytes) may be responsible for the overabundance of SPMs that we observed. The elevation of SPMs noted here appeared to be sex mediated, meaning that it was observed only in one sex (females). Given that SS primarily affects females (roughly 90% of diagnosed cases), these results may provide some insights into the mechanisms underlying the observed sexual dimorphism.

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“…Leukotriene D4 (LTD4) in particular has a strong affinity for cysteinyl leukotriene‐1 and promotes bronchial constriction, leaky vasculature and mucous production . Miyata et al noted that eosinophilic LTD4 production was significantly increased in nasal polyp tissue while 15‐LOX‐derived mediators were significantly reduced. Moreover, blood eosinophils of healthy subjects treated with eosinophil activators such as IL‐5 also produced a lipid profile similar to that of eosinophilic CRS.…”

Section: Precision Medicine In Crsmentioning

confidence: 99%

Novel findings in immunopathophysiology of chronic rhinosinusitis and their role in a model of precision medicine

Ong

Wang

2019

Allergy

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Our understanding of the pathophysiology of chronic rhinosinusitis (CRS) is continuously evolving. The traditional description of CRS in terms of two phenotypes based on the presence or absence of nasal polyps belies the underlying intricate immunopathophysiological processes responsible for this condition. CRS is being increasingly recognized as a disease spectrum encompassing a range of inflammatory states in the sinonasal cavity, with non-type 2 inflammatory disease on one end, type 2 inflammatory, eosinophil-heavy disease on the other and an overlap of both in different proportions in between. Abundance in research on the immune mechanisms of CRS has revealed various new endotypes that hold promise as biomarkers for the development of targeted therapies in severe, uncontrolled CRS. The introduction of precision medicine to manage this chronic, complex condition is a step forward in providing individualized care for all patients with CRS. In this review, the latest research on the pathophysiology of CRS with a focus on potential novel biomarkers and treatment options over the last 2 years are summarized and integrated into a suggested model of precision medicine in CRS. K E Y W O R D S biomarkers, chronic rhinosinusitis, endotypes, immunopathophysiology, precision medicine

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Dysregulated fatty acid metabolism in nasal polyp‐derived eosinophils from patients with chronic rhinosinusitis

Cited by 64 publications

References 45 publications

Dietary Omega-3 Fatty Acid Dampens Allergic Rhinitis via Eosinophilic Production of the Anti-Allergic Lipid Mediator 15-Hydroxyeicosapentaenoic Acid in Mice

Dietary Omega-3 Fatty Acid Dampens Allergic Rhinitis via Eosinophilic Production of the Anti-Allergic Lipid Mediator 15-Hydroxyeicosapentaenoic Acid in Mice

Sex‐mediated elevation of the specialized pro‐resolving lipid mediator levels in a Sjögren's syndrome mouse model

Novel findings in immunopathophysiology of chronic rhinosinusitis and their role in a model of precision medicine

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