scholarly journals GITRL on dendritic cells aggravates house dust mite-induced airway inflammation and airway hyperresponsiveness by modulating CD4+ T cell differentiation

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yaping Wang ◽  
Kou Liao ◽  
Bo Liu ◽  
Chao Niu ◽  
Wenjing Zou ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Differentiation ◽  
House Dust ◽  
House Dust Mite ◽  
Airway Hyperresponsiveness ◽  
T Cell Differentiation ◽  
Asthmatic Children ◽  
Dust Mite

Abstract Background Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) plays an important role in tumors, autoimmunity and inflammation. However, GITRL is not known to modulate the pathogenesis of allergic asthma. In this study, we investigated whether regulating GITRL expressed on dendritic cells (DCs) can prevent asthma and to elucidate its mechanism of action. Methods In vivo, the role of GITRL in modulating house dust mite (HDM)-induced asthma was assessed in adeno-associated virus (AAV)-shGITRL mice. In vitro, the role of GITRL expression by DCs was evaluated in LV-shGITRL bone marrow dendritic cells (BMDCs) under HDM stimulation. And the direct effect of GITRL was observed by stimulating splenocytes with GITRL protein. The effect of regulating GITRL on CD4+ T cell differentiation was detected. Further, GITRL mRNA in the peripheral blood of asthmatic children was tested. Results GITRL was significantly increased in HDM-challenged mice. In GITRL knockdown mice, allergen-induced airway inflammation, serum total IgE levels and airway hyperresponsiveness (AHR) were reduced. In vitro, GITRL expression on BMDCs was increased after HDM stimulation. Further, knocking down GITRL on DCs partially restored the balance of Th1/Th2 and Th17/Treg cells. Moreover, GITRL stimulation in vitro inhibited Treg cell differentiation and promoted Th2 and Th17 cell differentiation. Similarly, GITRL mRNA expression was increased in the peripheral blood from asthmatic children. Conclusions This study identified a novel role for GITRL expressed by DCs as a positive regulator of CD4+ T cells responses in asthma, which implicates that GITRL inhibitors may be a potential immunotherapy for asthma.

scholarly journals IL-25 Could Be Involved in the Development of Allergic Rhinitis Sensitized to House Dust Mite

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Dae Woo Kim ◽  
Dong-Kyu Kim ◽  
Kyoung Mi Eun ◽  
Jun-Sang Bae ◽  
Young-Jun Chung ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
House Dust ◽  
House Dust Mite ◽  
Allergic Inflammation ◽  
In Vitro Study ◽  
High Dose ◽  
Human Nasal Epithelial Cells ◽  
Dust Mite

Background and Purpose. When house dust mite (HDM), a common allergen, comes into the mucosal membrane, it may stimulate innate immunity. However, the precise role of interleukin- (IL-) 25 in the development of HDM-induced nasal allergic inflammation is still unclear. Therefore, we investigated the role of IL-25 in allergic rhinitis (AR) patients sensitized to HDM. Methods. To confirm the production of IL-25 in human nasal epithelial cells (HNECs), we stimulated HNECs. IL-25 expression in the nasal mucosa from control, non-AR (NAR) patients, and HDM-sensitized AR patients was assessed using immunohistochemistry, and quantitative reverse transcription PCR. Correlations between IL-25 and other inflammatory markers were explored. Results. An in vitro study showed significantly elevated concentrations of IL-25 in the HNEC samples with highest doses of HDM. Nasal tissues from AR patients sensitized to HDM showed significantly higher IL-25 expression, compared to those from the control or NAR patients. Moreover, the expression of IL-25 in nasal tissues from AR patients sensitized to HDM was positively associated with Th2 markers, such as ECP and GATA3. Conclusions. IL-25 expression increased with high-dose HDM stimulation and was related to Th2 markers. Therefore, IL-25 neutralization might offer a new strategy for treating patients with HDM-sensitized AR.

scholarly journals The role of house dust mite immunotherapy in Indonesian children with chronic rhinosinusitis allergy: A randomized control trial

Heliyon ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e06510
Author(s):  
Azwin Mengindra Putera ◽  
Zahrah Hikmah ◽  
Anang Endaryanto ◽  
Irwanto ◽  
Margarita Maria Maramis
Keyword(s):  
Chronic Rhinosinusitis ◽  
House Dust ◽  
House Dust Mite ◽  
Randomized Control Trial ◽  
Dust Mite ◽  
Randomized Control

scholarly journals Crucial role of stimulator of interferon genes-dependent signaling in house dust mite extract-induced IgE production

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroki Nunokawa ◽  
Yusuke Murakami ◽  
Takashi Ishii ◽  
Tomoya Narita ◽  
Haruyuki Ishii ◽  
...  
Keyword(s):  
B Cell ◽  
House Dust ◽  
House Dust Mite ◽  
Tfh Cells ◽  
Specific Serum ◽  
Mite Extract ◽  
Dust Mite ◽  
Cell Proportion ◽  
House Dust Mite Extract

AbstractStimulator of interferon genes (STING) is a DNA sensor that responds to pathogens and induces type I interferon production. Herein, the role of STING in house dust mite extract (HDM)-induced allergic asthma was investigated. C57BL/6 wild-type (WT) and Sting−/− mice were intratracheally sensitized with HDM, and the bronchoalveolar lavage fluid (BALF), sera, lungs, and mediastinal lymph nodes (MLNs) were analyzed. The total and HDM-specific serum IgE levels were lower in Sting−/− mice than in WT mice. B cell and IgE-positive B cell proportion in BALF and MLNs, respectively, was significantly lower in Sting−/− mice than in WT mice. Additionally, cyclic GMP-AMP, a STING ligand, augmented total and HDM-specific serum IgE levels and B cell proportion in BALF when applied in combination with HDM. To elucidate the role of STING in IgE production, follicular helper T (Tfh) cells, which are involved in B cell maturation, were investigated. Tfh cell proportion in MLNs decreased in Sting−/− mice, and IL-4 and IL-13 production by HDM-restimulated MLN cells from HDM-sensitized mice was decreased in Sting−/− mice compared with WT mice. Thus, STING plays an important role in the maturation and class switching of IgE-producing B cells in allergic inflammation via Tfh cells.

scholarly journals Oral Exposure to House Dust Mite Activates Intestinal Innate Immunity

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 561
Author(s):  
Sara Benedé ◽  
Leticia Pérez-Rodríguez ◽  
Mónica Martínez-Blanco ◽  
Elena Molina ◽  
Rosina López-Fandiño
Keyword(s):  
House Dust ◽  
House Dust Mite ◽  
Immune Cells ◽  
Oral Route ◽  
Innate Immune ◽  
Oral Exposure ◽  
Lymphoid Tissues ◽  
Innate Immune Cells ◽  
Dust Mite

Scope: House dust mite (HDM) induces Th2 responses in lungs and skin, but its effects in the intestine are poorly known. We aimed to study the involvement of HDM in the initial events that would promote sensitization through the oral route and eventually lead to allergy development. Methods and results: BALB/c mice were exposed intragastrically to proteolytically active and inactive HDM, as such, or in combination with egg white (EW), and inflammatory and type 2 responses were evaluated. Oral administration of HDM, by virtue of its proteolytic activity, promoted the expression, in the small intestine, of genes encoding tight junction proteins, proinflammatory and Th2-biasing cytokines, and it caused expansion of group 2 innate immune cells, upregulation of Th2 cytokines, and dendritic cell migration and activation. In lymphoid tissues, its proteolytically inactivated counterpart also exerted an influence on the expression of surface DC molecules involved in interactions with T cells and in Th2 cell differentiation, which was confirmed in in vitro experiments. However, in our experimental setting we did not find evidence for the promotion of sensitization to coadministered EW. Conclusion: Orally administered HDM upregulates tissue damage factors and also acts as an activator of innate immune cells behaving similarly to potent oral Th2 adjuvants.

scholarly journals Mast cell‐derived serotonin enhances methacholine‐induced airway hyperresponsiveness in house dust mite‐induced experimental asthma

Allergy ◽  
2021 ◽  
Author(s):  
Erika Mendez‐Enriquez ◽  
Perla Abigail Alvarado‐Vazquez ◽  
Willem Abma ◽  
Oscar E. Simonson ◽  
Sergey Rodin ◽  
...  
Keyword(s):  
Mast Cell ◽  
House Dust ◽  
House Dust Mite ◽  
Airway Hyperresponsiveness ◽  
Dust Mite
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