scholarly journals Group 2 Innate Lymphoid Cells and the House Dust Mite-Induced Asthma Mouse Model

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1178
Author(s):  
Yuichiro Yasuda ◽  
Tatsuya Nagano ◽  
Kazuyuki Kobayashi ◽  
Yoshihiro Nishimura
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
House Dust ◽  
Innate Lymphoid Cells ◽  
Airway Epithelial Cells ◽  
Lymphoid Cells ◽  
House Dust Mites ◽  
Airway Epithelial ◽  
Group 2 ◽  
Asthma Mouse Model

Asthma is an important issue not only in health but also in economics worldwide. Therefore, asthma animal models have been frequently used to understand the pathogenesis of asthma. Recently, in addition to acquired immunity, innate immunity has also been thought to be involved in asthma. Among innate immune cells, group 2 innate lymphoid cells (ILC2s) have been considered to be crucial for eosinophilic airway inflammation by releasing T helper 2 cytokines. Moreover, house dust mites (HDMs) belonging to group 1 act on airway epithelial cells not only as allergens but also as cysteine proteases. The production of interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP) from airway epithelial cells was induced by the protease activity of HDMs. These cytokines activate ILC2s, and activated ILC2s produce IL-5, IL-9, IL-13, and amphiregulin. Hence, the HDM-induced asthma mouse model greatly contributes to understanding asthma pathogenesis. In this review, we highlight the relationship between ILC2s and the HDM in the asthma mouse model to help researchers and clinicians not only choose a proper asthma mouse model but also to understand the molecular mechanisms underlying HDM-induced asthma.

scholarly journals Allergen protease-induced Gsdmd p40 controls IL-33 secretion

2021 ◽  
Author(s):  
Bing Sun ◽  
Bin Wu ◽  
Dong Wu ◽  
Feng Shao ◽  
Yaguang Zhang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Critical Role ◽  
Allergic Airway Inflammation ◽  
Airway Epithelial Cells ◽  
Allergen Exposure ◽  
Lymphoid Cells ◽  
House Dust Mites ◽  
Airway Epithelial ◽  
Group 2 ◽  
Inflammatory Caspases

Abstract Interleukin (IL)-33, an epithelial cell-derived cytokine that responds rapidly to environmental insult, has a critical role in initiating airway inflammation, such as that in asthma. However, the molecular mechanism underlying IL-33 secretion following allergen exposure is not clear. Here, we demonstrated that Gasdermin D (Gsdmd) functions as a conduit for IL-33 secretion following allergen protease exposure. Gsdmd was rapidly cleaved into a functional neo-form, the N-terminal p40 fragment (p40 NT-Gsdmd), in the murine airway epithelium when cells were exposed to allergen proteases from fungi, house dust mites (HDMs), or bacteria. This cleavage event that produces the p40 Gsdmd fragment was independent of inflammatory caspases-1/11, as it could not be inhibited by caspase-1 and caspase-11 deficiency in murine cells. The functional p40 NT-Gsdmd fragment directly contributed to the secretion of both the nuclear full-length form and cytosolic mature form of IL-33. Both Gsdmd deficiency and blockade of the generation of p40 by amino acid mutation or deletion of residues 308–313 (ELRQQ) in the Gsdmd sequence could efficiently prevent IL-33 release in airway epithelial cells. In mice, Gsdmd deficiency prevented IL-33 release and hindered the activation of group 2 innate lymphoid cells (ILC2s), thus alleviating airway inflammation and lung tissue damage after stimulation with HDMs or papain. Our findings uncovered a mechanism of Gsdmd-mediated IL-33 release under allergen exposure and offer insight into Gsdmd cleavage prevention as a potential approach to reduce allergic airway inflammation.

scholarly journals Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma

2021 ◽  
Vol 22 (9) ◽  
pp. 4369
Author(s):  
Corrado Pelaia ◽  
Giulia Pelaia ◽  
Claudia Crimi ◽  
Angelantonio Maglio ◽  
Luca Gallelli ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Human Monoclonal Antibody ◽  
Airway Epithelial Cells ◽  
Lymphoid Cells ◽  
Airway Epithelial ◽  
Airborne Pollutants ◽  
Group 2 ◽  
Efficacy Profile ◽  
Refractory Asthma

Thymic stromal lymphopoietin (TSLP) is an innate cytokine, belonging to the group of alarmins, which plays a key pathogenic role in asthma by acting as an upstream activator of cellular and molecular pathways leading to type 2 (T2-high) airway inflammation. Released from airway epithelial cells upon tissue damage induced by several noxious agents including allergens, viruses, bacteria, and airborne pollutants, TSLP activates dendritic cells and group 2 innate lymphoid cells involved in the pathobiology of T2-high asthma. Tezepelumab is a fully human monoclonal antibody that binds to TSLP, thereby preventing its interaction with the TSLP receptor complex. Preliminary results of randomized clinical trials suggest that tezepelumab is characterized by a good safety and efficacy profile in patients with severe, uncontrolled asthma.

scholarly journals Airway Epithelial Cells Are Crucial Targets of Glucocorticoids in a Mouse Model of Allergic Asthma

2017 ◽  
Vol 199 (1) ◽  
pp. 48-61 ◽  
Author(s):  
Carina Klaßen ◽  
Anna Karabinskaya ◽  
Lien Dejager ◽  
Sabine Vettorazzi ◽  
Justine Van Moorleghem ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Allergic Asthma ◽  
Airway Epithelial Cells ◽  
Airway Epithelial

House dust mite regulate the lung inflammation of asthmatic mice through TLR4 pathway in airway epithelial cells

2010 ◽  
Vol 28 (7) ◽  
pp. 597-603 ◽  
Author(s):  
Li Hongjia ◽  
Gai Qingling ◽  
Lin Meiying ◽  
Wang Weixuan ◽  
Zhang Lihong ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
House Dust ◽  
House Dust Mite ◽  
Lung Inflammation ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Dust Mite

scholarly journals The house dust mite allergen Der p 5 binds lipid ligands and stimulates airway epithelial cells through a TLR2-dependent pathway

2018 ◽  
Vol 49 (3) ◽  
pp. 378-390 ◽  
Author(s):  
Pinya Pulsawat ◽  
Tewarit Soongrung ◽  
Pattraporn Satitsuksanoa ◽  
Maxime Le Mignon ◽  
Souad Khemili ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
House Dust ◽  
House Dust Mite ◽  
Airway Epithelial Cells ◽  
Mite Allergen ◽  
Airway Epithelial ◽  
House Dust Mite Allergen ◽  
Dust Mite ◽  
Dust Mite Allergen ◽  
Dependent Pathway
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