Human Eosinophils Express a Distinct Gene Expression Program in Response to IL-3 Compared with Common β-Chain Cytokines IL-5 and GM-CSF

Nelson, Ryan K.; Brickner, Howard; Panwar, Bharat; Ramírez-Suástegui, Ciro; Mata, Sara Herrera de la; Liu, Neiman; Diaz, Damaris; Alexander, Laura E. Crotty; Ay, Ferhat; Vijayanand, Pandurangan; Seumois, Grégory; Akuthota, Praveen

doi:10.4049/jimmunol.1801668

Cited by 21 publications

(16 citation statements)

References 48 publications

(55 reference statements)

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“…First, GM-CSF participates in the resolution of in ammation, and IL-3 and IL-5 may also have such properties [10]. In addition, It has been reported that GM-CSF and IL-5 stimulation increase eosinophil gene expression [22]. Similar to IL-5, another cytokines including IL-3 and GM-CSF cytokines are produced as part of the Th2 in ammatory response and are crucial to eosinophil development and function.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Sambucus Ebulus Fruits Extract Ameliorates Eosinophilic Nasal Polyposis: An in vitro Study

Faghani¹,

Pourgholamali²,

Ansar³

et al. 2020

Preprint

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Background: The Sambucus Ebulus (ES) L. has an anti-inflammatory role by reducing the expression of pro-inflammatory genes and free radicals. The aim of this study was to evaluate the anti-inflammatory effect of hydroalcoholic extract of SE fruits on eosinophilic nasal polyposis (NP) in Vitro.Method: The chemical composition of SE fruits extract was determined by gas chromatography-mass spectrometry. Polyp Samples were collected from 40 patients and were cut into four pieces (control and case groups). Tissue fragments were treated with 0 (control), 50, 315 and 1000µg/ml of SE FRUIT extract in a culture medium for 24 hours. Apoptosis was detected by TUNEL reaction reagent. Real time-PCR was employed to evaluate the expression of Bax and Bad genes. ELISA was used for assay of IL-5 and GM-CSF.Results: Our findings showed SE fruits extract increased apoptosis in nasal polyp tissues compared to the control group (P<0.001). Also, GM-CSF level in the experimental groups was significantly lower than that in the control group (P<0.001). In contrast, the level of IL-5 was not significantly different in the treatment and control groups (P>0.05). Bax and Bad expression showed a significant increase in the experimental groups compared to the control group (P<0.001).Conclusion: Our findings showed that SE fruits hydroalcoholic extract ameliorates NP trough elevation of apoptosis and reduction of inflammatory markers. Our experimental data revealed that SE fruits extract plays an important role in the treatment of nasal polyp through inducing apoptosis and reducing the survival of inflammatory cells.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Sambucus Ebulus Fruits Extract Ameliorates Eosinophilic Nasal Polyposis: An in vitro Study

Faghani¹,

Pourgholamali²,

Ansar³

et al. 2020

Preprint

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“…Eosinophils were purified from peripheral blood of healthy donors by negative selection (StemCell Technologies, Vancouver, Canada) 29 and pretreated with 10 ng/mL interleukin (IL) 5 for 48-72 hours. Eosinophils were then added at a 1:1 ratio to monolayers of active EoE fibroblasts cultured in 4-well slide chambers untreated or prestimulated with 50 ng/mL LIGHT for 24 hours.…”

Section: Fibroblast-eosinophil Coculture Modelmentioning

confidence: 99%

Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype

et al. 2020

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BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is an antigen-mediated eosinophilic disease of the esophagus that involves fibroblast activation and progression to fibrostenosis. Cytokines produced by T-helper type 2 cells and transforming growth factor beta 1 (TGFb1) contribute to the development of EoE, but other cytokines involved in pathogenesis are unknown. We investigate the effects of tumor necrosis factor superfamily member 14 (TNFSF14, also called LIGHT) on fibroblasts in EoE. METHODS: We analyzed publicly available esophageal CD3 þ Tcell single-cell sequencing data for expression of LIGHT. Esophageal tissues were obtained from pediatric patients with EoE or control individuals and analyzed by immunostaining. Human primary esophageal fibroblasts were isolated from esophageal biopsy samples of healthy donors or patients with active EoE. Fibroblasts were cultured; incubated with TGFb1 and/or LIGHT; and analyzed by RNA sequencing, flow cytometry, immunoblots, immunofluorescence, or reverse transcription polymerase chain reaction. Eosinophils were purified from peripheral blood of healthy donors, incubated with interleukin 5, cocultured with fibroblasts, and analyzed by immunohistochemistry. RESULTS: LIGHT was up-regulated in the esophageal tissues from patients with EoE, compared with control individuals, and expressed by several T-cell populations, including T-helper type 2 cells. TNF receptor superfamily member 14 (TNFRSF14, also called HVEM) and lymphotoxin beta receptor

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“…IL-3, IL-5, and GM-CSF have similar effects on eosinophil adhesion and comparable efficacy to induce eosinophil transmigration through a layer of epithelial cells via the β2 integrin [8]. Due to the abovementioned properties, IL-3, IL-5, and GM-CSF are considered as a potential target in asthma therapeutics [27]; however, IL-5 was selected as a priority target to reduce eosinophilia because it is highly specific for eosinophilic inflammation [28].…”

Section: Role Of Eosinophilopoietins On Eosinophils Functionsmentioning

confidence: 99%

“…The IL-5 receptor is fairly specific since it is only expressed on eosinophils and basophils, while receptors for IL-3 and GM-CSF are present on many haematopoietic cells [28]. Despite all three cytokines sharing a standard beta (β) chain receptor subunit, each differentially affects eosinophils biology due to alpha (α) chain subunit-specific properties [27]. The cytokines attach to their respective α-chain with low affinity (nanomolar); on the other hand, subsequent recruitment of the β-chain contributes to a conformational change to a great affinity (picomolar) binding complex [8].…”

Section: Role Of Eosinophilopoietins On Eosinophils Functionsmentioning

confidence: 99%

“…Phase 2, randomised placebo-controlled trial to evaluate the efficacy and safety of an anti-GM-CSF antibody in patients with inadequately controlled asthma results show that FEV1 in prespecified groups of participants treated with anti-GM-CSF compared with placebo showed improvements in patients with eosinophilic asthma [62]. There is evidence that IL-3 through alpha subunit-specific properties uniquely influences eosinophil biology and may serve as a potential therapeutic target also [27].…”

Section: Role Of Integrins On Eosinophils Functionsmentioning

confidence: 99%

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The role of eosinophilopoietins and integrins on eosinophils biology in asthma

Palačionytė¹,

Januškevičius²,

Malakauskas³

2020

PIA

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Asthma is a chronic inflammatory airway disease that affects about 300 million peopleworldwide, and the incidence is continuously increasing. Patientswith asthma aremost commonly diagnosedwith type 2 inflammation,which is characterized by eosinophilia, which is an increased amount of eosinophils in the blood and airways. Asthma with predominant eosinophilic inflammation is characterized by amore severe course of the disease,more frequent exacerbations, andmore intense symptoms. To reduce symptoms, facilitate the course of the disease, and treat asthma more effectively is important to understand asthma pathogenesis better. Eosinophils survivalmaturation, activation, and quantity in the lungs are promoted by cytokines, of which eosinophilopoietins – interleukin (IL) 3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) are themost important. Eosinophilia is also associated with the activation of integrins present on the surface of eosinophils. Integrins areresponsible for eosinophils adhesion to airway structural cells, thus prolonging their survival leading to more intense airway eosinophilia. Eosinophilopoietins, their receptors, and integrins might be suitable targets reducing eosinophilia in blood and airway, as well as airway inflammation.Humanizedmonoclonal antibodies are used for this purpose. Biological therapy allows for the specific inhibition of relevant asthma pathways and offers patients individualized treatment. This review will discuss the biological significance of eosinophilopoietins and their receptors, integrins on eosinophils functions, anti-cytokine and anti-integrin therapy efficiency in asthma.

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Human Eosinophils Express a Distinct Gene Expression Program in Response to IL-3 Compared with Common β-Chain Cytokines IL-5 and GM-CSF

Cited by 21 publications

References 48 publications

WITHDRAWN: Sambucus Ebulus Fruits Extract Ameliorates Eosinophilic Nasal Polyposis: An in vitro Study

WITHDRAWN: Sambucus Ebulus Fruits Extract Ameliorates Eosinophilic Nasal Polyposis: An in vitro Study

Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype

The role of eosinophilopoietins and integrins on eosinophils biology in asthma

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