Interleukin-31 expression and relation to disease severity in human asthma

Lai, Tianwen; Wu, Dong; Li, Wen; Chen, Min; Yi, Zhennan; Huang, Dan; Jing, Zhiliang; Lǚ, Yingying; Lv, Quanchao; Li, Dongming; Wu, Bin

doi:10.1038/srep22835

Cited by 39 publications

(46 citation statements)

References 25 publications

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“…Patients with severe asthma showed higher expression of IL-31 and IL-31R in bronchial tissue compared with those with mild disease or with controls. High IL-31 serum levels in asthmatic patients positively correlated with those ofTh2 cytokines (IL-5, IL-13, and thymic stromal lymphopoietin) [33]. Those results demonstrate a role for IL-31 in asthma pathogenesis that must be clarified by future studies.…”

Section: The Il-31/il-31r Axis and Inflammatory Diseasesmentioning

confidence: 59%

“…Expression of IL-31 was recently investigated in serum, bronchoalveolar lavage fluid, and bronchial tissue from patients with allergic asthma vs. controls [33]. The former individuals displayed higher IL-31 serum and bronchoalveolar lavage fluid levels than the latter did [33]. Patients with severe asthma showed higher expression of IL-31 and IL-31R in bronchial tissue compared with those with mild disease or with controls.…”

Section: The Il-31/il-31r Axis and Inflammatory Diseasesmentioning

confidence: 99%

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The IL-31/IL-31 receptor axis: general features and role in tumor microenvironment

Ferretti

Corcione

Pistoia

2017

Journal of Leukocyte Biology

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IL-31 is a recently identified cytokine with a well-defined role in the pathogenesis of pruritus. IL-31, whose production is induced by IL-4 and IL-33, binds a heterodimeric receptor (R) composed of the exclusive IL-31RA chain and the shared oncostatin M R. Signaling through the IL-31R involves the MAPK, PI3K/AKT and Jak/STAT pathways. Different variants and isoforms of IL-31RA with different signaling activities have been identified. IL-31 is produced predominantly by circulating Th2 lymphocytes and skin-homing CLACD45RO T cells. Studies in humans have demonstrated a pathogenic role for IL-31 in atopic dermatitis and allergic asthma. The first demonstration of the involvement of the IL-31/IL-31R axis in cancer came from studies in patients with mycosis fungoides/Sézary syndrome, the most frequent, cutaneous T cell lymphoma. Tumor cells were shown to produce IL-31, whose serum levels correlated with pruritus intensity. Follicular lymphoma (FL) B cells and their counterparts-germinal center B cells-produced IL-31 and expressed IL-31R, which signaled in the former, but not the latter, cells. IL-31 released in association with microvesicles promoted tumor growth through autocrine/paracrine loops. Malignant mast cells from patients with mastocytosis or Philadelphia-negative myeloproliferative disorder produced IL-31, which contributed to pruritus pathogenesis. Finally, patients with endometrial carcinoma displayed high serum levels of IL-31 and IL-33, which may represent promising disease biomarkers. Targeting strategies for the IL-31/IL-31R axis have been developed, including the CIMM331 humanized anti-human IL-31RA antibody recently tested in a phase I/Ib study.

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Section: The Il-31/il-31r Axis and Inflammatory Diseasesmentioning

confidence: 59%

Section: The Il-31/il-31r Axis and Inflammatory Diseasesmentioning

confidence: 99%

The IL-31/IL-31 receptor axis: general features and role in tumor microenvironment

Ferretti

Corcione

Pistoia

2017

Journal of Leukocyte Biology

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“…5B,C). IL31 is of major interest to our study as it is a Th2 cytokine overexpressed in asthma 35,36 . As such, IL31 was further analysed by real-time PCR in the complete set of www.nature.com/scientificreports www.nature.com/scientificreports/ PBMC samples, including healthy controls and asthmatic subjects to establish whether IL31 was indeed subject to regulation by WNT5A.…”

Section: Induced Wnt5a Expression Increases Production Of Th2-cytokinmentioning

confidence: 99%

Smooth-muscle-derived WNT5A augments allergen-induced airway remodelling and Th2 type inflammation

Koopmans

Hesse

Nawijn

et al. 2020

Sci Rep

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Asthma is a heterogeneous disease characterized by chronic inflammation and structural changes in the airways. The airway smooth muscle (ASM) is responsible for airway narrowing and an important source of inflammatory mediators. We and others have previously shown that WNT5A mRNA and protein expression is higher in the ASM of asthmatics compared to healthy controls. Here, we aimed to characterize the functional role of (smooth muscle-derived) WNT5A in asthma. We generated a tet-ON smooth-muscle-specific WNT5A transgenic mouse model, enabling in vivo characterization of smoothmuscle-derived WNT5A in response to ovalbumin. Smooth muscle specific WNT5A overexpression showed a clear trend towards enhanced actin (α-SMA) expression in the ASM in ovalbumin challenged animals, but had no effect on collagen content. WNT5A overexpression in ASM also significantly enhanced the production of the Th2-cytokines IL4 and IL5 in lung tissue after ovalbumin exposure. In line with this, WNT5A increased mucus production, and enhanced eosinophilic infiltration and serum IgE production in ovalbumin-treated animals. In addition, CD4 + T cells of asthma patients and healthy controls were stimulated with WNT5A and changes in gene transcription assessed by RNA-seq. WNT5A promoted expression of 234 genes in human CD4 + T cells, among which the Th2 cytokine IL31 was among the top 5 upregulated genes. IL31 was also upregulated in response to smooth muscle-specific WNT5A overexpression in the mouse. In conclusion, smooth-muscle derived WNT5A augments Th2 type inflammation and remodelling. Our findings imply a pro-inflammatory role for smooth musclederived WNT5A in asthma, resulting in increased airway wall inflammation and remodelling. Asthma is a heterogeneous disease characterized by chronic inflammation of the large and small airways. More than 200 million people worldwide are estimated to be affected by asthma 1. Asthma is characterized by episodic changes in respiratory symptoms such as breathlessness, wheezing, chest tightness and coughing, reflecting airway hyper-responsiveness (AHR). Apart from this variable component of AHR, asthma is characterized by the development of structural changes in the airways, termed airway remodelling, which contribute to airflow obstruction 2. Airway smooth muscle (ASM) is a central player in the pathology of asthma. Airway smooth muscle thickness correlates with asthma severity and lung function 3. In line with this, bronchial thermoplasty (BT) results in diminished ASM mass in severe asthmatics for up to at least two years 4 , which is associated with improvement in quality of life, and a reduction in symptoms and number of exacerbations 5. ASM cells are major

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“…In other work, the IL-6 family member oncostatin M, levels of which are increased in bronchoalveolar lavage (BAL) fluid of allergic asthmatic patients, reduced airway epithelial integrity by disrupting TJ assembly but did not influence the production of TJ components. 41 The related cytokine, IL-31, expression of which is also increased in the airways of asthmatic patients with severe disease, 42 has likewise been implicated in barrier dysfunction (Fig 2). Secretion of this novel cytokine by T H 2 cells requires autocrine IL-4.…”

Section: Innate Cytokines That Promote Th2-driven Asthma At the Epithmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

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Interleukin-31 expression and relation to disease severity in human asthma

Cited by 39 publications

References 25 publications

The IL-31/IL-31 receptor axis: general features and role in tumor microenvironment

The IL-31/IL-31 receptor axis: general features and role in tumor microenvironment

Smooth-muscle-derived WNT5A augments allergen-induced airway remodelling and Th2 type inflammation

Pathogenic CD4 + T cells in patients with asthma

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