Arachidonic Acid Directly Activates the Human DP2 Receptor.

Aberrant type 2 inflammatory responses are the underlying cause of the pathophysiology of allergic asthma, allergic rhinitis, and other atopic diseases, with an alarming prevalence in relevant parts of the Western world. A bulk of evidence points out the important role of the DP2 receptor in these inflammation processes. A screening of different polyunsaturated fatty acids at a fluorescence resonance energy transfer-based DP2 receptor conformation sensor expressed in human embryonic kidney (HEK) cells revealed an agonistic effect of the prostaglandin (PG)-D precursor arachidonic acid on DP2 receptor activity of about 80% of the effect induced by PGD In a combination of experiments at the conformation sensor and using a bioluminescence resonance energy transfer-based G protein activation sensor expressed together with DP2 receptor wild type in HEK cells, we found that arachidonic acid acts as a direct activator of the DP2 receptor, but not the DP1 receptor, in a concentration range considered physiologically relevant.

BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells.

Recent studies reveal a critical role of tumor cell-released extracellular vesicles (EVs) in pancreatic cancer (PC) progression. However, driver genes that direct EV function, the EV-recipient cells, and their cellular response to EV uptake remain to be identified. Therefore, we studied the role of Bcl-2-associated-anthanogene 6 (BAG6), a regulator of EV biogenesis for cancer progression.

Reciprocal crosstalk between Th17 and mesothelial cells promotes metastasis-associated adhesion of ovarian cancer cells.

Background: IL-17A and TNF synergistically promote inflammation and tumorigenesis. Their interplay and impact on ovarian carcinoma (OC) progression are, however, poorly understood. We addressed this question focusing on mesothelial cells, whose interaction with tumor cells is known to play a pivotal role in transcoelomic metastasis formation.

Mutual Regulation of Transcriptomes between Murine Pneumocytes and Fibroblasts Mediates Alveolar Regeneration in Air-Liquid Interface Cultures.

Alveolar type 2 and club cells are part of the stem cell niche of the lung and their differentiation is required for pulmonary homeostasis and tissue regeneration. A disturbed crosstalk between fibroblasts and epithelial cells contributes to the loss of lung structure in chronic lung diseases. Therefore, it is important to understand how fibroblasts and lung epithelial cells interact during regeneration.

Epithelial-immune cell interactions in allergic diseases.

Epithelial/immune interactions are characterized by the different properties of the various epithelial tissues, the mediators involved, and the varying immune cells that initiate, sustain, or abrogate allergic diseases on the surface. The intestinal mucosa, respiratory mucosa, and regular skin feature structural differences according to their primary function and surroundings. In the context of these specialized functions, the active role of the epithelium in shaping immune responses is increasingly recognizable.

Type 2 T-Cell Responses against Distinct Epitopes of the Desmoglein 3 Ectodomain in Pemphigus Vulgaris.

Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin and/or mucous membranes caused by IgG autoantibodies that predominantly target two transmembrane desmosomal cadherins: desmoglein (DSG)1 and DSG3. DSG-specific T cells play a central role in PV pathogenesis because they provide help to autoreactive B cells for autoantibody production. In this study, we characterized DSG3-specific peripheral T cells in a cohort of 52 patients with PV and 41 healthy controls with regard to cytokine profile and epitope specificity.

Human Lung Organoids-A Novel Experimental and Precision Medicine Approach.

The global burden of respiratory diseases is very high and still on the rise, prompting the need for accurate models for basic and translational research. Several model systems are currently available ranging from simple airway cell cultures to complex tissue-engineered lungs. In recent years, human lung organoids have been established as highly transferrable three-dimensional in vitro model systems for lung research.

Identification of extracellular vesicle microRNA signatures specifically linked to inflammatory and metabolic mechanisms in obesity-associated low type-2 asthma.

Rationale And Objective: Plasma extracellular vesicles (EVs) represent a vital source of molecular information about health and disease states. Due to their heterogenous cellular sources, EVs and their cargo may predict specific pathomechanisms behind disease phenotypes. Here we aimed to utilize EV microRNA (miRNA) signatures to gain new insights into underlying molecular mechanisms of obesity-associated low type-2 asthma.

Improved automatic identification of isolated rapid eye movement sleep behavior disorder with a 3D time-of-flight camera.

Background And Purpose: Automatic 3D video analysis of the lower body during rapid eye movement (REM) sleep has been recently proposed as a novel tool for identifying people with isolated REM sleep behavior disorder (iRBD), but, so far, it has not been validated on unseen subjects. This study aims at validating this technology in a large cohort and at improving its performances by also including an analysis of movements in the head, hands and upper body.

Methods: Fifty-three people with iRBD and 128 people without RBD (of whom 89 had sleep disorders considered RBD differential diagnoses) were included in the study.

The emerging role of extracellular vesicles as communicators between adipose tissue and pathologic lungs with a special focus on asthma.

Extracellular vesicles (EVs) gain increasing attention due to their (patho-)physiological role in intercellular signaling, specifically in the communication between distant organs. Recent studies highlight a connection between the adipose tissue (AT) and the lung via (immuno-)modulatory EVs in disorders such as obesity-associated asthma and lung cancer-associated cachexia. Although lung cancer-derived EVs induce lipolysis and myotube atrophy in vivo, pathogenic effects were also reported in the opposite direction with the involvement of AT-derived EVs in cancer-promoting responses and potentially in asthma development.

Intranasal administration of Acinetobacter lwoffii in a murine model of asthma induces IL-6-mediated protection associated with cecal microbiota changes.

Background: Early-life exposure to certain environmental bacteria including Acinetobacter lwoffii (AL) has been implicated in protection from chronic inflammatory diseases including asthma later in life. However, the underlying mechanisms at the immune-microbe interface remain largely unknown.

Methods: The effects of repeated intranasal AL exposure on local and systemic innate immune responses were investigated in wild-type and Il6 , Il10 , and Il17 mice exposed to ovalbumin-induced allergic airway inflammation.

Timing of Blood Sample Processing Affects the Transcriptomic and Epigenomic Profiles in CD4 T-cells of Atopic Subjects.

Optimal pre-analytical conditions for blood sample processing and isolation of selected cell populations for subsequent transcriptomic and epigenomic studies are required to obtain robust and reproducible results. This pilot study was conducted to investigate the potential effects of timing of CD4 T-cell processing from peripheral blood of atopic and non-atopic adults on their transcriptomic and epigenetic profiles. Two heparinized blood samples were drawn from each of three atopic and three healthy individuals.

TeaSpam: A Novel Method of TEmporal And SPAtial Movement Encoding during Sleep.

Movements during sleep characterize sleep disorders, which can disturb sleep or its onset, impacting sleep quantity and quality. Video-polysomnography is the current gold standard to assess movements during sleep, but its availability is limited. Using data recorded with a 3D time of flight sensor, we developed a novel method of encoding temporal and spatial information of automatically identified movements during sleep.

Single-cell RNA sequencing uncovers the nuclear decoy lincRNA PIRAT as a regulator of systemic monocyte immunity during COVID-19.

The systemic immune response to viral infection is shaped by master transcription factors, such as NF-κB, STAT1, or PU.1. Although long noncoding RNAs (lncRNAs) have been suggested as important regulators of transcription factor activity, their contributions to the systemic immunopathologies observed during SARS-CoV-2 infection have remained unknown.

Local and Systemic Production of Pro-Inflammatory Eicosanoids Is Inversely Related to Sensitization to Aeroallergens in Patients with Aspirin-Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by overproduction of the pro-inflammatory eicosanoids. Although immunoglobulin E-mediated sensitization to aeroallergens is common among AERD patients, it does not belong to the defining disease characteristics. In this study of 133 AERD patients, we sought to find a relationship between sensitization to aeroallergens and local (leukotriene E, prostaglandin E and prostaglandin D) and/or systemic (leukotriene E) production of arachidonic acid metabolites.

Side-Directed Release of Differential Extracellular Vesicle-associated microRNA Profiles from Bronchial Epithelial Cells of Healthy and Asthmatic Subjects.

Extracellular vesicles (EVs) are released by virtually all cells and may serve as intercellular communication structures by transmitting molecules such as proteins, lipids, and nucleic acids between cells. MicroRNAs (miRNAs) are an abundant class of vesicular RNA playing a pivotal role in regulating intracellular processes. In this work, we aimed to characterize vesicular miRNA profiles released in a side-directed manner by bronchial epithelial cells from healthy and asthmatic subjects using an air-liquid interface cell culture model.

Automatic 3D Video Analysis of Upper and Lower Body Movements to Identify Isolated REM Sleep Behavior Disorder: A Pilot Study.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment, abnormal jerks and movements during REM sleep. Isolated RBD (iRBD) is recognized as the early stage of alpha-synucleinopathies, i.e.

Functional (un-)Coupling: Impairment, Compensation, and Future Progression in Alzheimer's Disease.

Functional (un-)coupling (task-related change of functional connectivity) between different sites of the brain is a mechanism of general importance for cognitive processes. In Alzheimer's disease (AD), prior research identified diminished cortical connectivity as a hallmark of the disease. However, little is known about the relation between the amount of functional (un-)coupling and cognitive performance and decline in AD.

Differential Regulation of Interferon Signaling Pathways in CD4 T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype.

In the era of personalized medicine, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as asthma phenotypes including obesity-associated asthma, are urgently needed. Peripheral blood was drawn from 10 obese, non-atopic asthmatic adults with a high body mass index (BMI; 36.67 ± 6.

Mitogen-activated protein kinase signaling in childhood asthma development and environment-mediated protection.

Background: While childhood asthma prevalence is rising in Westernized countries, farm children are protected. The mitogen-activated protein kinase (MAPK) pathway with its negative regulator dual-specificity phosphatase-1 (DUSP1) is presumably associated with asthma development.

Objectives: We aimed to investigate the role of MAPK signaling in childhood asthma and its environment-mediated protection, including a representative selection of 232 out of 1062 children from two cross-sectional cohorts and one birth cohort study.

Epigenetic Mechanisms in Allergy Development and Prevention.

There has been a substantial increase in the incidence and the prevalence of allergic disorders in the recent decades, which seems to be related to rapid environmental and lifestyle changes, such as higher exposure to factors thought to exert pro-allergic effects but less contact with factors known to be associated with protection against the development of allergies. Pollution is the most remarkable example of the former, while less contact with microorganisms, lower proportion of unprocessed natural products in diet, and others resulting from urbanization and westernization of the lifestyle exemplify the latter. It is strongly believed that the effects of environmental factors on allergy susceptibility and development are mediated by epigenetic mechanisms, i.