scholarly journals Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Noelle Zurmühl ◽  
Anna Schmitt ◽  
Ulrike Formentini ◽  
Johannes Weiss ◽  
Heike Appel ◽  
...  

Abstract Background Human plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood. Methods This in vitro study on human pDC isolated from peripheral blood was designed to compare side by side the uptake of three clinically relevant representative allergens: fluorochrome-labeled house dust mite Der p 1, Bee venom extract from Apis mellifera (Api) and the food allergen OVA analyzed flow cytometry and confocal microscopy. Results We found that the internalization and its regulation by TLR9 ligation was significantly different between allergens in terms of time course and strength of uptake. Api and OVA uptake in pDC of healthy subjects was faster and reached higher levels than Der p 1 uptake. CpG ODN 2006 suppressed OVA uptake and to a lesser extent Der p 1, while Api internalization was not affected. All allergens colocalized with LAMP1 and EEA1, with Api being internalized particularly fast and reaching highest intracellular levels in pDC. Of note, we could not determine any specific differences in antigen uptake in allergic compared with healthy subjects. Conclusions To our knowledge this is the first study that directly compares uptake regulation of clinically relevant inhalative, injective and food allergens in pDC. Our findings may help to explain differences in the onset and severity of allergic reactions as well as in the efficiency of AIT.

2018 ◽  
Vol 8 (1) ◽  
pp. 20-26
Author(s):  
Asim Rizvi ◽  
Sean T. Fitzgerald ◽  
Kent D. Carlson ◽  
Dan Dragomir Daescu ◽  
Waleed Brinjikji ◽  
...  

Background: “Remote aspiration,” using suction from the proximal internal carotid artery (ICA) to open terminus occlusions, has been reported in small case series. However, it remains unclear whether remote aspiration is feasible for middle cerebral artery occlusions in the setting of potential inflow from communicating arteries. We performed an in vitro study to assess whether suction applied at various locations proximal to an occlusion could successfully aspirate the clot. Methods: A glass model of 4 mm inner diameter (ID) with 1 mm distal narrowing and 2 mm side branch to simulate a communicating artery was constructed. A proximal side branch was placed to simulate inflow from the proximal ICA. The impact of three different-sized catheters (ID 0.088, 0.070, and 0.056 in) on histologically different (red blood cell-cell rich, fibrin-rich, and mixed) clot analogues was tested with the catheter tip placed remotely either distal or proximal to the collateral branch. Aspiration was attempted with (1) open system (flow in both the ICA and the collateral branch, (2) flow arrest with open collateral (no flow in the ICA, but flow in the collateral branch), and (3) closed system (no flow in either the ICA or the collateral branch). The outcome was success or failure of remote aspiration. Results: For the 0.088-in catheter, remote aspiration was successful in all conditions. For the 0.070-in catheter, remote aspiration was unsuccessful without proximal flow arrest, but was successful in all other scenarios. For the 0.056-in catheter, remote aspiration was successful only with complete flow arrest. Conclusions: In a noncollapsible system, remote aspiration can be successfully achieved even in the setting of prominent branch arteries by using relatively large aspiration catheters. Proximal flow arrest may facilitate successful remote aspiration for some catheter sizes.


Rheumatology ◽  
2018 ◽  
Vol 58 (4) ◽  
pp. 617-627 ◽  
Author(s):  
Sijia Chen ◽  
Troy Noordenbos ◽  
Iris Blijdorp ◽  
Leonieke van Mens ◽  
Carmen A Ambarus ◽  
...  

Abstract Objectives Synovial mast cells contain IL-17A, a key driver of tissue inflammation in SpA. A recent in vitro study showed that tissue-derived mast cells can capture and release exogenous IL-17A. The present study aimed to investigate if this mechanism could contribute to tissue inflammation in SpA. Methods Potential activation of mast cells by IL-17A was assessed by gene expression analysis of the Laboratory of Allergic Diseases 2 (LAD2) mast cell line. The presence of IL-17A-positive mast cells was assessed by immunohistochemistry in synovial tissue obtained before and after secukinumab treatment, as well as in skin and gut tissues from SpA-related conditions. Results IL-17A did not induce a pro-inflammatory response in human LAD2 mast cells according to the canonical IL-17A signalling pathway. In SpA synovial tissue, the percentage of IL-17A-positive mast cells increased upon treatment with secukinumab. IL-17A-positive mast cells were also readily detectable in non-inflamed barrier tissues such as skin and gut. In non-inflamed dermis and gut submucosa, IL-17A-positive mast cells are the most prevalent IL-17A-positive cells in situ. Compared with non-inflamed tissues, both total mast cells and IL-17A-positive mast cells were increased in psoriatic skin dermis and in submucosa from inflammatory bowel disease gut. In contrast, the proportion of IL-17A-positive mast cells was strikingly lower in the inflamed compared with non-inflamed gut lamina propria. Conclusion IL-17A-positive mast cells are present across SpA target tissues and correlate inversely with inflammation, indicating that their IL-17A content can be regulated. Tissue-resident mast cells may act as IL-17A-loaded sentinel cells, which release IL-17A to amplify tissue inflammation.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Shiyao Xue ◽  
Hongdong Han ◽  
Shunli Rui ◽  
Mengliu Yang ◽  
Yizhou Huang ◽  
...  

Previous studies on serum fetuin-B (fetuin-like protein IRL685) have investigated its association with T2DM; however, the reason for the variation in serum fetuin-B and its regulatory factors in metabolic disease remain unclear. Here, we evaluated serum fetuin-B levels in women with newly diagnosed MetS and performed multiple interventions to investigate the role of fetuin-B in the pathogenesis of MetS. Serum fetuin-B levels were assessed using ELISA. Bioinformatics analysis was performed to analyze fetuin-B-related genes and signaling pathways. Additionally, oxidative stress parameters were measured in the in vitro study. For subgroup analyses, we performed EHC, OGTT, and treatment with a GLP-1RA to investigate the regulatory factors of serum fetuin-B. We found that in comparison with healthy subjects, serum fetuin-B levels were markedly increased in women with MetS. Further, serum fetuin-B showed a positive correlation with WHR, FAT%, TG, FBG, HbA1c, FIns, HOMA-IR, VAI, and LAP. Bioinformatics analysis revealed that most fetuin-B-related core genes were involved in cholesterol metabolism and fat decomposition. Consistent with this finding, multivariate regression analysis showed that triglyceride content and WHR were independently associated with serum fetuin-B. We also observed that serum fetuin-B levels were markedly elevated in healthy subjects after glucose loading and in women with MetS during EHC. In vitro, overexpression of fetuin-B promoted oxidative stress in HepG2 cell. After 6 months of treatment with a GLP-1RA, serum fetuin-B levels in women with MetS decreased following an improvement in metabolism and insulin sensitivity. Therefore, serum fetuin-B is associated with MetS, which may serve as a biomarker of oxidative stress. This trial is registered with ChiCTR-OCC-11001422.


2014 ◽  
Vol 56 (8) ◽  
pp. 655-659 ◽  
Author(s):  
Chang-Young Lee ◽  
Seong-Ho Park ◽  
Chang-Hyun Kim ◽  
Goetz Benndorf

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2806 ◽  
Author(s):  
Evdokia K. Mitsou ◽  
Georgia Saxami ◽  
Emmanuela Stamoulou ◽  
Evangelia Kerezoudi ◽  
Eirini Terzi ◽  
...  

Alterations of gut microbiota are evident during the aging process. Prebiotics may restore the gut microbial balance, with β-glucans emerging as prebiotic candidates. This study aimed to investigate the impact of edible mushrooms rich in β-glucans on the gut microbiota composition and metabolites by using in vitro static batch culture fermentations and fecal inocula from elderly donors (n = 8). Pleurotus ostreatus, P. eryngii, Hericium erinaceus and Cyclocybe cylindracea mushrooms derived from various substrates were examined. Gut microbiota composition (quantitative PCR (qPCR)) and short-chain fatty acids (SCFAs; gas chromatography (GC)) were determined during the 24-h fermentation. P. eryngii induced a strong lactogenic effect, while P. ostreatus and C. cylindracea induced a significant bifidogenic effect (p for all <0.05). Furthermore, P. eryngii produced on wheat straw and the prebiotic inulin had comparable Prebiotic Indexes, while P. eryngii produced on wheat straw/grape marc significantly increased the levels of tested butyrate producers. P. ostreatus, P. eryngii and C. cylindracea had similar trends in SCFA profile; H. erinaceus mushrooms were more diverse, especially in the production of propionate, butyrate and branched SCFAs. In conclusion, mushrooms rich in β-glucans may exert beneficial in vitro effects in gut microbiota and/or SCFAs production in elderly subjects.


2020 ◽  
Vol 47 (8) ◽  
pp. 3691-3702 ◽  
Author(s):  
Elisabeth Mara ◽  
Monika Clausen ◽  
Suphalak Khachonkham ◽  
Simon Deycmar ◽  
Clara Pessy ◽  
...  

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