Human Mast Cell Sensitization with IgE Increases miRNA-210 Expression

Just, Jesper; Ipsen, Pernille Munk; Kruhøffer, Mogens; Lykkemark, Simón; Skjold, Tina; Schiøtz, Peter Oluf; Hoffmann, Hans‐Jürgen

doi:10.1159/000496513

Cited by 10 publications

(7 citation statements)

References 14 publications

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“…The miRs detected comprise previously reported miRs in the context of asthma, such as miR-15b-5p, whose systemic levels are associated with lung function, 39 miR-16-5p, whose circulating levels correlated with hyper-responsiveness of the airways, 18,40,41 miR-19a-3p, which has been reported to be expressed in local T cells, 42 and miR-21-3p, which was found in exhaled breath condensate from asthmatics, however in reduced levels compared to healthy controls. 43 addition, we detected elevated levels of miR-191-5p, the serum levels of which also correlated with lung function, measured with FEV 1 /FVC, in a recent paediatric study, 39 and miR-210-3p, which is involved in mast cell activation, 44 and, finally, miR-223-3p, which was increased in asthmatics compared to healthy controls and correlated with lung function parameters. 45 It has further been published that miR-223-3p is involved in the maturation and function of neutrophils.…”

Section: Known Allergy-associated Mirs Detected In the Lower Airwayssupporting

confidence: 59%

Sputum microRNA‐screening reveals Prostaglandin EP3 receptor as selective target in allergen‐specific immunotherapy

Jakwerth

Chaker

Guerth

et al. 2021

Clin Experimental Allergy

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Background Several microRNAs (miRs) have been described as potential biomarkers in liquid biopsies and in the context of allergic asthma, while therapeutic effects on the airway expression of miRs remain elusive. In this study, we investigated epigenetic miR‐associated mechanisms in the sputum of grass pollen‐allergic patients with and without allergen‐specific immunotherapy (AIT). Methods Induced sputum samples of healthy controls (HC), AIT‐treated and ‐untreated grass pollen‐allergic rhinitis patients with (AA) and without asthma (AR) were profiled using miR microarray and whole‐transcriptome microarray analysis of the same samples. miR targets were predicted in silico and used to identify inverse regulation. Local PGE2 levels were measured using ELISA. Results Two hundred and fifty nine miRs were upregulated in the sputum of AA patients compared with HC, while only one was downregulated. The inverse picture was observed in induced sputum of AIT‐treated patients: while 21 miRs were downregulated, only 4 miRs were upregulated in asthmatics upon AIT. Of these 4 miRs, miR‐3935 stood out, as its predicted target PTGER3, the prostaglandin EP3 receptor, was downregulated in treated AA patients compared with untreated. The levels of its ligand PGE2 in the sputum supernatants of these samples were increased in allergic patients, especially asthmatics, and downregulated after AIT. Finally, local PGE2 levels correlated with ILC2 frequencies, secreted sputum IL‐13 levels, inflammatory cell load, sputum eosinophils and symptom burden. Conclusions While profiling the sputum of allergic patients for novel miR expression patterns, we uncovered an association between miR‐3935 and its predicted target gene, the prostaglandin E3 receptor, which might mediate AIT effects through suppression of the PGE2‐PTGER3 axis.

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Section: Known Allergy-associated Mirs Detected In the Lower Airwayssupporting

confidence: 59%

Sputum microRNA‐screening reveals Prostaglandin EP3 receptor as selective target in allergen‐specific immunotherapy

Jakwerth

Chaker

Guerth

et al. 2021

Clin Experimental Allergy

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“…We previously stated that spontaneous as well as CCL5‐ and TNF‐induced migration of IgE‐coated mast cells was significantly higher than the migration of native mast cells 47 . Interestingly, a recent report also documented that mast cell sensitization with IgE increases the expression level of microRNA‐210 48 . There are also some data indicating that IgE sensitization affects mast cell response mediated by TLRs.…”

Section: Discussionmentioning

confidence: 98%

“…47 Interestingly, a recent report also documented that mast cell sensitization with IgE increases the expression level of microRNA-210. 48 There are also some data indicating that IgE sensitization affects mast cell response mediated by TLRs. For example, IgE-dependent sensitization induces higher TNF secretion by bone marrow-derived mast cells (BMMCs) than nonsensitized cells in response to LPS, which is a well-known TLR4 ligand.…”

Section: Discussionmentioning

confidence: 99%

Mannan activates tissue native and IgE-sensitized mast cells to proinflammatory response and chemotaxis in TLR4-dependent manner

Żelechowska

Brzezińska‐Błaszczyk

Różalska

et al. 2020

Journal of Leukocyte Biology

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Mast cells take part in host defense against microorganisms as they are numerous at the portal of infection, exert several essential mechanisms of pathogen destruction, and they express pattern recognition receptors. Accumulating evidence indicates that these cells are involved in the control and clearance of bacterial, viral, or parasitic infections, but much less is known about their contribution in defense against fungi. The study was aimed to establish whether mannan, which comprises an outermost layer and major structural constituent of the fungal cell wall, may directly stimulate tissue mast cells to the antifungal response. Our findings indicate that mannan activates mast cells isolated from the rat peritoneal cavity to initiate the proinflammatory response.We found that mannan stimulates mast cells to release histamine and to generate cysteinyl leukotrienes, cytokines (IFN-, GM-CSF, TNF), and chemokines (CCL2, CCL3). It also increased the mRNA expression of various cytokines/chemokines. We also documented that mannan strongly activates mast cells to generate reactive oxygen species and serves as a potent chemoattractant for these cells. Furthermore, we established that mannan-induced activity of mast cells is mediated via TLR4 with the involvement of the spleen tyrosine kinase molecule. Taking together, our results clearly support the idea that mast cells act as sentinel cells and crucially determine the course of the immune response during fungal infection. Additionally, presented data on IgE-coated mast cells suggest that exposure to fungal mannan could influence the severity of IgE-dependent diseases, including allergic ones.

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“…Furthermore, miR-223-3p was elevated in asthmatics compared to healthy controls and correlated with lung function parameters ( 36 ). MiR-210-3p has been shown to be involved in mast cell activation ( 78 ), while miR-223-3p is involved in neutrophil maturation and function by inhibiting IL-18 expression in macrophages, suggesting a fine-tuned mechanism involving inflammatory IL-18-induced neutrophil extracellular traps (NETs) ( 79 ).…”

Section: Non-coding Rnas Of Immune Cells In Type-2 Diseasesmentioning

confidence: 99%

Role of microRNAs in type 2 diseases and allergen-specific immunotherapy

et al. 2022

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MicroRNAs (miRs) have gained scientific attention due to their importance in the pathophysiology of allergic diseases as well as their potential as biomarkers in allergen-specific treatment options. Their function as post-transcriptional regulators, controlling various cellular processes, is of high importance since any single miR can target multiple mRNAs, often within the same signalling pathway. MiRs can alter dysregulated expression of certain cellular responses and contribute to or cause, but in some cases prevent or repress, the development of various diseases. In this review article, we describe current research on the role of specific miRs in regulating immune responses in epithelial cells and specialized immune cells in response to various stimuli, in allergic diseases, and regulation in the therapeutic approach of allergen-specific immunotherapy (AIT). Despite the fact that AIT has been used successfully as a causative treatment option since more than a century, very little is known about the mechanisms of regulation and its connections with microRNAs. In order to fill this gap, this review aims to provide an overview of the current knowledge.

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Human Mast Cell Sensitization with IgE Increases miRNA-210 Expression

Cited by 10 publications

References 14 publications

Sputum microRNA‐screening reveals Prostaglandin EP3 receptor as selective target in allergen‐specific immunotherapy

Sputum microRNA‐screening reveals Prostaglandin EP3 receptor as selective target in allergen‐specific immunotherapy

Mannan activates tissue native and IgE-sensitized mast cells to proinflammatory response and chemotaxis in TLR4-dependent manner

Role of microRNAs in type 2 diseases and allergen-specific immunotherapy

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