Mechanism of interleukin‐25 (IL‐17E)‐induced pulmonary inflammation and airways hyper‐reactivity

Sharkhuu, Tuya; Matthaei, Klaus I.; Forbes, Elizabeth; Mahalingam, Suresh; Hogan, Simon P.; Hansbro, Philip M.; Foster, Paul S.

doi:10.1111/j.1365-2222.2006.02595.x

Cited by 95 publications

(89 citation statements)

References 27 publications

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“…Transgenic expression of IL-25 in the bronchial epithelium results in mucus production and recruitment of macrophages and eosinophils to the airways (39). Similarly, intranasal instillation of recombinant IL-25 promotes AHR, eosinophilic inflammation, mucus hypersecretion, and production of Th2-type cytokines in the lung (41). In contrast, blockade of IL-25 reduces airway inflammation and Th2 cytokine production in an acute allergen-induced asthma model (39,42).…”

Section: Discussionmentioning

confidence: 94%

“…Although IL-25 does not directly induce smooth muscle contraction, stimulation of cells with IL-25 increases their expression of components of the extracellular matrix, namely procollagen-a1 and lumican mRNA (44). Instillation of a single dose of IL-25 to the airways of mice has been shown to result in AHR, which is maintained for at least 16 days (41). Conversely, blocking IL-25 in an acute experimental model of allergic asthma has been demonstrated to prevent AHR (42).…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of Smad2 Drives House Dust Mite–mediated Airway Remodeling and Airway Hyperresponsiveness via Activin and IL-25

Gregory

Mathie

Walker

et al. 2010

Am J Respir Crit Care Med

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Rationale: Airway hyperreactivity and remodeling are characteristic features of asthma. Interactions between the airway epithelium and environmental allergens are believed to be important in driving development of pathology, particularly because altered epithelial gene expression is common in individuals with asthma. Objectives: To investigate the interactions between a modified airway epithelium and a common aeroallergen in vivo. Methods: We used an adenoviral vector to generate mice overexpressing the transforming growth factor-b signaling molecule, Smad2, in the airway epithelium and exposed them to house dust mite (HDM) extract intranasally. Measurements and Main Results: Smad2 overexpression resulted in enhanced airway hyperreactivity after allergen challenge concomitant with changes in airway remodeling. Subepithelial collagen deposition was increased and smooth muscle hyperplasia was evident resulting in thickening of the airway smooth muscle layer. However, there was no increase in airway inflammation in mice given the Smad2 vector compared with the control vector. Enhanced airway hyperreactivity and remodeling did not correlate with elevated levels of Th2 cytokines, such as IL-13 or IL-4. However, mice overexpressing Smad2 in the airway epithelium showed significantly enhanced levels of IL-25 and activin A after HDM exposure. Blocking activin A with a neutralizing antibody prevented the increase in lung IL-25 and inhibited subsequent collagen deposition and also the enhanced airway hyperreactivity observed in the Smad2 overexpressing HDM-exposed mice. Conclusions: Epithelial overexpression of Smad2 can specifically alter airway hyperreactivity and remodeling in response to an aeroallergen. Moreover, we have identified novel roles for IL-25 and activin A in driving airway hyperreactivity and remodeling.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Overexpression of Smad2 Drives House Dust Mite–mediated Airway Remodeling and Airway Hyperresponsiveness via Activin and IL-25

Gregory

Mathie

Walker

et al. 2010

Am J Respir Crit Care Med

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“…Although classic animal models of experimental asthma depend on sensitized Th2 cells, intranasal administration of IL-25 or IL-33 in mice have also been reported to induce an asthma phenotype with airway hyperresponsiveness, eosinophilic inflammation, mucus hypersecretion, and Th2 cytokine production in the lung [14,25,34]. Since ILC2s are reported to release cytokines in response to IL-25 or IL-33 stimulation [7,9], we hypothesized that pulmonary ILC2s contribute to airway inflammation in cytokineinduced asthma.…”

Section: Pulmonary Ilc2s Are Induced In Il-25-and Il-33-induced Asthmamentioning

confidence: 99%

Pulmonary innate lymphoid cells are major producers of IL‐5 and IL‐13 in murine models of allergic asthma

et al. 2012

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Allergic asthma is characterized by chronic airway inflammation and hyperreactivity and is thought to be mediated by an adaptive T helper-2 (Th2) cell-type immune response. Here, we demonstrate that type 2 pulmonary innate lymphoid cells (ILC2s) significantly contribute to production of the key cytokines IL-5 and IL-13 in experimental asthma. In naive mice, lineage-marker negative ILC2s expressing IL-7Rα, CD25, Sca-1, and T1/ST2(IL-33R) were present in lungs and mediastinal lymph nodes (MedLNs) , IntroductionAllergic asthma is characterized by a predominant eosinophilic airway inflammation, airway hyperreactivity, and a chronic T helper-2 (Th2) cell-type of immune response to various allergens, such as house dust mites (HDMs), molds, or animal dander [1,2]. Available experimental models for asthma indicate that allergenspecific Th2 cells are key players in induction and maintenance of allergic asthma [3]. These cells produce vast amounts of cytokines Correspondence: Dr. Rudi W. Hendriks e-mail: r.hendriks@erasmusmc.nl that induce IgE synthesis (IL-4), recruit eosinophils and mast cells (via IL-5 and IL-9, respectively), and cause smooth muscle hyperreactivity via ).Although adaptive Th2 cells have been identified as important sources of IL-4, , many recent studies emphasize the importance of innate cells in cytokine production, including but not limited to mast cells, eosinophils, and basophils. Next to the canonical NK and lymphoid-tissue inducer (LTi) cells, a growing family of cytokine-producing "helper" innate lymphoid cells (ILCs) has been identified [6]. Interestingly, a lineage-negative ILC population that produces high amounts of IL-5 and IL-13 was identified in fat-associated lymphoid clusters (FALCs) andwww.eji-journal.eu Eur. J. Immunol. 2012. 42: 1106-1116 Immunomodulation 1107 mesenteric lymph nodes [7][8][9]. These cells were named natural helper cells, nuocytes, or multipotent progenitors and, because of their Th2 cytokine production, they have been dubbed type 2 ILCs [6]. ILC2s play a role in defense mechanisms and (re)shaping immune and nonimmune tissues and can be stimulated with IL-25 and IL-33. In a Nocardia brasiliensis infection model, ILC2s were essential and sufficient for clearance of this helminth from the mucosa, even in the absence of the adaptive immune system [7,9]. Recently, various groups demonstrated the presence of ILC2s in the respiratory system of mice and humans [10][11][12]. ILC2 were shown to accumulate in the lungs of mice after infection with influenza virus, via an IL-33 dependent mechanism. These ILC2 induced airway hyperreactivity through IL-13 secretion [10] and also restored airway epithelial integrity and lung function and contributed to airway remodeling by the production of amphiregulin [12]. In addition, ILC2s were found in nasal polyps of patients with chronic rhinitis, a classical Th2 disease [11].IL-25 is a member of the IL-17 cytokine family that is expressed in human and mouse in response to allergens, particles, and helminth infection [13][14][15]. Administ...

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“…150,154 IL-17E-induced mucous hypersecretion and AHR have been suggested to be primarily dependent on IL-13-STAT6 signaling. 150,155 In addition to the induction of Th2 cytokines, one study showed that prolonged IL-17 expression in the lung induced NKT cell-dependent pulmonary arterial remodelling. 156 IL-17E also contributes to VEGF signaling-induced angiogenesis via the Erk/MAPK and PI3K/Akt pathways in 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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Mechanism of interleukin‐25 (IL‐17E)‐induced pulmonary inflammation and airways hyper‐reactivity

Cited by 95 publications

References 27 publications

Overexpression of Smad2 Drives House Dust Mite–mediated Airway Remodeling and Airway Hyperresponsiveness via Activin and IL-25

Overexpression of Smad2 Drives House Dust Mite–mediated Airway Remodeling and Airway Hyperresponsiveness via Activin and IL-25

Pulmonary innate lymphoid cells are major producers of IL‐5 and IL‐13 in murine models of allergic asthma

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

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