IL-25 drives remodelling in allergic airways disease induced by house dust mite

Gregory, Lisa G.; Jones, Carla P.; Walker, Simone A.; Sawant, Devika; Gowers, Kate H.C.; Campbell, Gaynor A.; McKenzie, Andrew N. J.; Lloyd, Clare M.

doi:10.1136/thoraxjnl-2012-202003

Cited by 159 publications

(170 citation statements)

References 31 publications

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“…Using a house dust mite allergen stimulation model in adult mice, and with the coadministration of an adenoviral vector expressing Smad2 to enhance a remodelling phenotype, Gregory and colleagues reported that anti-IL-25 abrogated peribronchial collagen deposition and airway hyperreactivity (62). This correlated with a moderate reduction of TRANSATLANTIC AIRWAY CONFERENCE IL-5 and IL-13 and a more profound decrease in IL-33 and TSLP.…”

Section: Ilc2 In Lung Allergy and Inflammationmentioning

confidence: 90%

Type-2 Innate Lymphoid Cells in Asthma and Allergy

McKenzie

2014

Annals ATS

115

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Type-2 innate lymphoid cells (ILC2) belong to an expanding family of innate lymphocytes that provide a potent source of immune effector cytokines at the initiation of immune responses. ILC2 arise, under the control of the transcription factors RORa and GATA3, from lymphoid progenitors in the bone marrow, to secrete type-2 cytokines including IL-5 and IL-13. Using experimental models, ILC2 have been implicated in allergic diseases, such as asthma and atopic dermatitis, but also in metabolic homeostasis. Furthermore, recent reports have indicated that ILC2 not only play roles at the initiation of type-2 immunity but can also contribute to chronic pathology, such as fibrosis, and can impact on the priming of the adaptive T-cell response. The identification of ILC2 in patients with allergic dermatitis and allergic rhinitis indicates that these cells may represent new therapeutic targets.Keywords: type-2 immunity; type-2 innate lymphoid cells; innate immunity; cytokines However, a recent major paradigm shift has added another layer of complexity to immunoregulation by cytokines with the discovery of innate lymphoid cells (ILCs) (2). ILCs produce many Th cell-associated cytokines but do not express cell surface markers associated with other immune cell lineages (lineage-negative [Lin 2 ]) and do not express a T-cell receptor. The ILC family now includes ILC1 (predominantly IFN-g-expressing cells), ILC2 (predominantly IL-5-and IL-13-expressing cells), and ILC3 (predominantly IL-22-and IL-17-expressing cells) (3-6). Due to their recent discovery, our knowledge of these cells is still rather rudimentary, but major roles are emerging for ILCs in protective immunity against parasitic helminths (ILC2) (7-9) and bacteria (ILC1 and ILC3) (10-12), and in autoimmune disorders (ILC1 and ILC3) (13), allergic disease (ILC2) (14-16), and obesity (17)(18)(19).Recent comprehensive reviews have described the identification and phenotypic characterization of 20). This review focuses on the most recent advances in our understanding of the factors that regulate ILC2 development and how these cells contribute to allergy and lung inflammation. ILC2ILC2 are found in the blood, spleen, intestine, liver, lung, fat-associated lymphoid clusters, and lymph nodes of mice (7-9). They are Lin 2 (CD3CD4CD8CD19CD11bCD11cFceR1 NK1.1Gr1 2 ) CD45 1 CD127

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Section: Ilc2 In Lung Allergy and Inflammationmentioning

confidence: 90%

Type-2 Innate Lymphoid Cells in Asthma and Allergy

McKenzie

2014

Annals ATS

115

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“…157 Moreover, blocking IL-17E in the airways of allergenFunctional mechanisms of IL-17 family cytokines X Song et al challenged mice decreases the deposition of peribronchial collagen and the hyperplasia of airway smooth muscles. 158 IL-17E contributes to allergenic resources by orchestrating airway remodelling in addition to inducing airway type 2 inflammation. Thus, IL-17B shows opposing phenotypes to IL-17E during allergic asthma.…”

Section: Il-17dmentioning

confidence: 99%

The roles and functional mechanisms of interleukin-17 family cytokines in mucosal immunity

et al. 2016

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The mucosal immune system serves as our front-line defense against pathogens. It also tightly maintains immune tolerance to self-symbiotic bacteria, which are usually called commensals. Sensing both types of microorganisms is modulated by signalling primarily through various pattern-recognition receptors (PRRs) on barrier epithelial cells or immune cells. After sensing, proinflammatory molecules such as cytokines are released by these cells to mediate either defensive or tolerant responses. The interleukin-17 (IL-17) family members belong to a newly characterized cytokine subset that is critical for the maintenance of mucosal homeostasis. In this review, we will summarize recent progress on the diverse functions and signals of this family of cytokines at different mucosal edges.

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“…Our data showed that both IL-25 and OVAchallenged mice showed increased production of both mediators, first in the lung parenchyma and in the airways lumen, with a time course reflecting that of elevated blood vessel signature markers including vWF and ERG. vWF is a common marker for evaluating angiogenesis in vivo and ex vivo [12], while ERG is a member of the ETS (erythroblast transformation-specific) family of transcription factors which is selectively expressed by endothelial cells, specific haematopoetic cells and pre-cartilage cells. It has been shown that ERG plays an important role in blood vessel homeostasis and angiogenesis by regulating a variety of endothelial cellular functions including survival, junctional stability and migration [26].…”

Section: Discussionmentioning

confidence: 99%

“…In mice, overexpression or exogenous administration of IL-25 produces an asthma-like inflammatory response, including increased serum IgE production, blood eosinophilia and lung eosinophilic infiltrates, epithelial cell hyperplasia/hypertrophy, increased mucus secretion and airways hyperreactivity [8][9][10][11]. Conversely, blockade of IL-25 remarkably reduced Th2 cytokine production and airways inflammation [7,12], and in addition ameliorated airways remodelling changes including peribronchial collagen deposition and smooth muscle hyperplasia, with corresponding reduction of hyperreactivity [12].…”

Section: Introductionmentioning

confidence: 99%

IL-25 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma model

Yao¹,

Wang²,

Huang³

et al. 2015

5.3 Allergy and Immunology

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Background: Th2-promoting cytokine IL-25 might contribute to bronchial mucosal vascular remodelling in asthma through its receptor expressed by vascular endothelial and vascular smooth muscle cells. Methods: By utilising a newly established chronic asthma murine model induced by direct exposure of the airways to IL-25 alone, we examined effects of IL-25 on angiogenesis, vascular remodelling and expression of angiogenic factors, compared changes with those in a "classical" ovalbumin (OVA)-induced murine asthma model. IL-25 and OVA were intranasally instilled into the airways of BALB/c mice for up to 55 days. Airways vessels and angiogenic factors, including Von Willebrand Factor (vWF), amphiregulin, angiogenin, endothelin-1, transcription factor ERG, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor (IGF-1) and vascular endothelial growth factor (VEGF) in lung sections, homogenates and BAL fluid were detected and quantified by immunostaining or enzyme linked immunosorbent assay (ELISA). An in house assay was also utilised to compare the effects of IL-25 and other Th2-cytokines on angiogenesis by human vascular endothelial cells. Results: Repetitive intranasal challenge with IL-25 alone or OVA alone in OVA-presensitised animals significantly increased peribronchial vWF + vessels in the murine airways, which was associated with remarkably elevated expression of amphiregulin, angiogenin, endothelin-1, bFGF, EGF, IGF-1, VEGF and ERG. IL-25, but not Th-2-cytokines induced human angiogenesis in vitro. Conclusions: The data suggest that chronic exposure of murine airways to IL-25 alone is able to reproduce a local angiogenic milieu. Thus, blocking IL-25 may attenuate vascular remodelling and improve outcomes in asthma patients.

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IL-25 drives remodelling in allergic airways disease induced by house dust mite

Cited by 159 publications

References 31 publications

Type-2 Innate Lymphoid Cells in Asthma and Allergy

Type-2 Innate Lymphoid Cells in Asthma and Allergy

The roles and functional mechanisms of interleukin-17 family cytokines in mucosal immunity

IL-25 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma model

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