Two single nucleotide polymorphisms in TSLP gene are associated with asthma susceptibility in Chinese Han population

Li, Wen; Xu, Li-Sheng; Liu, Qiji; Dong, Fangzheng; Qiu, Rongfang; Wen, Mingchun; Han, Yanxiao; Tang, Ningbo; Kang, Lijun; Wu, Jinxiang; Liu, Fen; Zhao, Jiping; Yong, Yang; Wang, Junfei; Ding, Mingjie; Sun, Yuemei; Fei, Wen-Jian; Dong, Liang

doi:10.3109/01902148.2012.714840

Cited by 26 publications

(17 citation statements)

References 24 publications

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“…TSLP can induce multiple signaling pathways in asthma, including STAT6, IL-4 [55], IL-1β and TNFα [56], p38 and Jun kinase (JNK ). The central role of Stat3/5 in TSLP-signaling pathway has also been unveiled [57]. Here we further explored the signaling pathway in TSLP-induced airway remodeling in asthma.…”

Section: Discussionmentioning

confidence: 95%

Central Role of Cellular Senescence in TSLP-Induced Airway Remodeling in Asthma

Dong

Wang

et al. 2013

PLoS ONE

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BackgroundAirway remodeling is a repair process that occurs after injury resulting in increased airway hyper-responsiveness in asthma. Thymic stromal lymphopoietin (TSLP), a vital cytokine, plays a critical role in orchestrating, perpetuating and amplifying the inflammatory response in asthma. TSLP is also a critical factor in airway remodeling in asthma.ObjectivesTo examine the role of TSLP-induced cellular senescence in airway remodeling of asthma in vitro and in vivo.MethodsCellular senescence and airway remodeling were examined in lung specimens from patients with asthma using immunohischemical analysis. Both small molecule and shRNA approaches that target the senescent signaling pathways were used to explore the role of cellular senescence in TSLP-induced airway remodeling in vitro. Senescence-Associated β-galactosidase (SA-β-Gal) staining, and BrdU assays were used to detect cellular senescence. In addition, the Stat3-targeted inhibitor, WP1066, was evaluated in an asthma mouse model to determine if inhibiting cellular senescence influences airway remodeling in asthma.ResultsActivation of cellular senescence as evidenced by checkpoint activation and cell cycle arrest was detected in airway epithelia samples from patients with asthma. Furthermore, TSLP-induced cellular senescence was required for airway remodeling in vitro. In addition, a mouse asthma model indicates that inhibiting cellular senescence blocks airway remodeling and relieves airway resistance.ConclusionTSLP stimulation can induce cellular senescence during airway remodeling in asthma. Inhibiting the signaling pathways of cellular senescence overcomes TSLP-induced airway remodeling.

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Section: Discussionmentioning

confidence: 95%

Central Role of Cellular Senescence in TSLP-Induced Airway Remodeling in Asthma

Dong

Wang

et al. 2013

PLoS ONE

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“…Thymic stromal lymphopoietin (TSLP) is a cytokine released by epithelial cells critically regulating the activation of dendritic cells (DC) and subsequent Th2 immune responses in asthma. Liu et al 22 analysed the polymorphism of the two SNP Rs2289276 and Rs2289278 in TSLP gene and evaluated the association between the two SNP and asthma susceptibility in Chinese Han population using a case-control study. They found that the genotype and allele frequencies of the two SNP in asthma patients were significantly different from those in the healthy controls.…”

Section: Gene Susceptibility Of Asthmamentioning

confidence: 99%

Asthma research in China: A five‐year review

2013

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Asthma is one of the most common chronic diseases worldwide with increasing morbidity. China has the largest asthmatic population and is one of the countries with the highest asthma mortality. Fortunately, asthma research in China, both clinical and scientific, has developed markedly over the past few years. This has resulted in significant increases in our understanding of Chinese asthma prevalence, risk factors, control status, pathogenesis, and new prevention or treatment strategies. In this review, the major achievements of asthma research in China from 2008 to 2012 are summarized.

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“…This is because type 2 helper T cell (Th2)-mediated inflammatory responses primed by activated DCs, are pivotal for the onset of widespread allergic diseases of the airways, skin and gut8. In fact, TSLP is now widely considered to underlie some of the most prevalent inflammatory allergic disorders, such as the atopic diseases (asthma, atopic dermatitis and atopic rhinitis), chronic obstructive pulmonary disease (COPD) and eosinophilic esophagitis9101112, and has been annotated as a genetic risk factor for the development of asthma131415 and eosinophilic esophagitis16. Furthermore, a staggering 70% of atopic dermatitis clinical cases go on to develop asthma via the ‘allergic march' (also known as ‘atopic march')17, and adult asthmatics are strongly predisposed for acquiring COPD (ref.…”

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confidence: 99%

Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma

et al. 2017

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The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) is pivotal to the pathophysiology of widespread allergic diseases mediated by type 2 helper T cell (Th2) responses, including asthma and atopic dermatitis. The emergence of human TSLP as a clinical target against asthma calls for maximally harnessing its therapeutic potential via structural and mechanistic considerations. Here we employ an integrative experimental approach focusing on productive and antagonized TSLP complexes and free cytokine. We reveal how cognate receptor TSLPR allosterically activates TSLP to potentiate the recruitment of the shared interleukin 7 receptor α-chain (IL-7Rα) by leveraging the flexibility, conformational heterogeneity and electrostatics of the cytokine. We further show that the monoclonal antibody Tezepelumab partly exploits these principles to neutralize TSLP activity. Finally, we introduce a fusion protein comprising a tandem of the TSLPR and IL-7Rα extracellular domains, which harnesses the mechanistic intricacies of the TSLP-driven receptor complex to manifest high antagonistic potency.

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Two single nucleotide polymorphisms in TSLP gene are associated with asthma susceptibility in Chinese Han population

Abstract: TSLP variants are significantly associated with bronchial asthma. TSLP might be a new therapeutic target molecule for asthma.

Cited by 26 publications

References 24 publications

Central Role of Cellular Senescence in TSLP-Induced Airway Remodeling in Asthma

Central Role of Cellular Senescence in TSLP-Induced Airway Remodeling in Asthma

Asthma research in China: A five‐year review

Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma

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