IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways

Kearley, Jennifer; Erjefält, Jonas; Andersson, Cecilia; Benjamin, Emelia J.; Jones, Carla P.; Robichaud, Annette; Pégorier, Sophie; Brewah, Yambasu A.; Burwell, Timothy; Bjermer, Leif; Kiener, Peter A.; Kolbeck, Roland; Lloyd, Clare M.; Coyle, Anthony J.; Humbles, Alison A.

doi:10.1164/rccm.200909-1462oc

Cited by 185 publications

(175 citation statements)

References 55 publications

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“…However, the mechanism how IL-9 works on ICCs remains unclear. A possible theory about the mechanism may be that IL-9 promotes the proliferation and SCF secretion of mast cells [22] . Then SCF combines with the c-Kit on the surface of ICCs and results in the activation of downstream signaling pathways, which regulate the growth and repair of ICCs [23] .…”

Section: Discussionmentioning

confidence: 99%

Effects of Exogenous Interleukin-9 on the Growth, Proliferation and Activity of Interstitial Cells of Cajal Cultured in vitro

Huang

Du²,

Gong³

et al. 2016

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Objectives: To evaluate the role of exogenous interleukin-9 (IL-9) in the growth, proliferation and activity of interstitial cells of Cajal (ICCs) cultured in vitro, and to assess its role in maintaining the functions of ICCs. Methods: ICCs of murine gastric antrum were isolated and cultured in vitro. ICCs were identified with c-Kit and ANO1 immunofluorescent antibodies. Both fluorescence microscope and confocal microscopy were used to observe the effects of IL-9 on the growth, proliferation and activity of ICCs in cultured in vitro. ICCs were loaded with fluorescence probe Fluo-3/AM and the fluorescence of intracellular calcium concentration ([Ca²⁺]_i) was measured by confocal microscopy. The effects of exogenous IL-9 on the sulfated cholecystokinin octapeptide (CCK-8S)-evoked [Ca²⁺]_i elevation were observed by confocal microscopy. Results: Immunofluorescence results confirmed the successful separation and culture of ICCs in vitro. IL-9 in concentrations ranging from 0.02 to 1 μg/ml promoted the growth, proliferation and activity of ICCs in culture, and ICCs grew best with 0.5 mg/ml of IL-9. The presence of IL-9 could significantly increase the CCK-8S-evoked [Ca²⁺]_i oscillation, which is probably caused by facilitating the maintenance of the functions of ICCs under suitable conditions for culture. Conclusion: IL-9 could promote the growth, proliferation and activity of ICCs, reinforce the CCK-8S-induced [Ca²⁺]_i increment in ICCs, and facilitate the maintenance of the functions of ICCs under suitable culture condition.

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Section: Discussionmentioning

confidence: 99%

Effects of Exogenous Interleukin-9 on the Growth, Proliferation and Activity of Interstitial Cells of Cajal Cultured in vitro

Huang

Du²,

Gong³

et al. 2016

Digestion

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“…Studies have shown that IL-9 is involved in the pathogenesis of human asthma (8,10,22,(37)(38)(39)(40). Indeed, monoclonal antibodies to IL-9 are currently being evaluated in asthma clinical trials (41).…”

Section: Human Th9 Cell Differentiation Is Also Regulated By Cox-2-dementioning

confidence: 99%

“…CD4 1 T helper cell subsets, which include T helper cell type 1 (Th1), Th2, and Th17 cells, are key components of the adaptive immune response in rodents and humans (1,(5)(6)(7). Allergic responses in the lung are traditionally thought of as being Th2 mediated; however, recent studies have shown that IL-9 contributes to allergic responses by promoting mast cell expansion and production of IL-13, which stimulates the release of mucus and contributes to airway hyperresponsiveness (1,5,8,9). Serum IL-9 levels, which correlate with symptom severity in patients with allergic rhinitis, depend on exposure to a causal allergen (10)(11)(12)(13)(14).…”

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confidence: 99%

Cyclooxygenase-2 Inhibits T Helper Cell Type 9 Differentiation during Allergic Lung Inflammation via Down-regulation of IL-17RB

Li¹,

Edin²,

Bradbury³

et al. 2013

Am J Respir Crit Care Med

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Rationale: HelperCD41 T cell subsets, includingIL-9-and IL-10-producing T helper cell type 9 (Th9) cells, exist under certain inflammatory conditions. Cyclooxygenase (COX)-1 and COX-2 play important roles in allergic lung inflammation and asthma. It is unknown whether COX-derived eicosanoids regulate Th9 cells during allergic lung inflammation. Objectives: To determine the role of COX metabolites in regulating Th9 cell differentiation and function during allergic lung inflammation., COX-2 2/2 , and wild-type (WT) mice were studied in an in vivo model of ovalbumin-induced allergic inflammation and an in vitro model of Th9 differentiation using flow cytometry, cytokine assays, confocal microscopy, real-time PCR, and immunoblotting. In addition, the role of specific eicosanoids and their receptors was examined using synthetic prostaglandins (PGs), selective inhibitors, and siRNA knockdown. Measurements and Main Results: Experimental endpoints were not different between COX-1 2/2 and WT mice; however, the percentage of IL-9 1 CD4 1 T cells was increased in lung, bronchoalveolar lavage fluid, lymph nodes, and blood of allergic COX-2 2/2 mice relative to WT. Bronchoalveolar lavage fluid IL-9 and IL-10, serum IL-9, and lung IL-17RB levels were significantly increased in allergic COX-2 2/2 mice or in WT mice treated with COX-2 inhibitors. IL-9, IL-10, and IL-17RB expression in vivo was inhibited by PGD 2 and PGE 2 , which also reduced Th9 cell differentiation of murine and human naive CD4 1 T cells in vitro. Inhibition of protein kinase A significantly increased Th9 cell differentiation of naive CD4 1 T cells isolated from WT mice in vitro. Conclusions: COX-2-derived PGD 2 and PGE 2 regulate Th9 cell differentiation by suppressing IL-17RB expression via a protein kinase A-dependent mechanism.

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“…IL-9 functions in multiple potential asthmatic roles, from promoting mast cell growth and development to initiating IL-4 expression and subsequent Bcell production of allergic antibodies. IL-9 has also been evaluated for its use as an asthma biomarker given its heightened expression in the lungs of asthmatic patients [61].…”

Section: Interleukinsmentioning

confidence: 99%

Protein Biomarkers in Asthma

Karaulov

Garib

et al. 2018

Int Arch Allergy Immunol

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Asthma is a chronic disabling respiratory disease that can be triggered by a variety of factors, including allergens, respiratory infections, psychological factors, occupational agents, exercise, atmospheric pollutants, and drugs. The asthma syndrome has been treated for decades according to a “one-fits-all” treatment strategy based on bronchodilators and steroids. With the availability of new forms of treatment targeting the different pathomechanisms of the asthma syndrome, such as anti-immunoglobulin E and cytokine-targeting therapies, the interest in biomarkers that can dis criminate different forms of asthma according to their pathomechanisms has increased. This review attempts to provide an overview of protein biomarkers in asthma and how they might be used to discriminate different forms of asthma that may respond positively to sophisticated new targeted therapies.

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IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways

Cited by 185 publications

References 55 publications

Effects of Exogenous Interleukin-9 on the Growth, Proliferation and Activity of Interstitial Cells of Cajal Cultured in vitro

Effects of Exogenous Interleukin-9 on the Growth, Proliferation and Activity of Interstitial Cells of Cajal Cultured in vitro

Cyclooxygenase-2 Inhibits T Helper Cell Type 9 Differentiation during Allergic Lung Inflammation via Down-regulation of IL-17RB

Protein Biomarkers in Asthma

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