A5061292311- Asthma and respiratory diseases
- Respiratory and Cough-Related Research
- Mast cells and histamine
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Pediatric health and respiratory diseases
- Food Allergy and Anaphylaxis Research
- Eosinophilic Disorders and Syndromes
- Allergic Rhinitis and Sensitization
- Biochemical Analysis and Sensing Techniques
- Immune Cell Function and Interaction
- Inflammatory mediators and NSAID effects
- Eicosanoids and Hypertension Pharmacology
- Analytical Chemistry and Chromatography
- Receptor Mechanisms and Signaling
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Fatty Acid Research and Health
- Olfactory and Sensory Function Studies
- Neuropeptides and Animal Physiology
- Antimicrobial Peptides and Activities
- Mass Spectrometry Techniques and Applications
- Protein Hydrolysis and Bioactive Peptides
- Advanced Chemical Sensor Technologies
- Immune Response and Inflammation
- Infant Nutrition and Health
Karolinska Institutet
2015-2025
Karolinska University Hospital
2023-2025
Swedish Asthma and Allergy Association
2012-2023
Institute for Asthma and Allergy
2015
AstraZeneca (Sweden)
2010
Lund University
2010
The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing migratory properties tonsil blood ILCs, signatures tissue-residency, activation modified metabolism colon lung ILCs. Trajectory revealed potential...
Specific inflammatory pathways are indicated to contribute severe asthma, but their individual involvement in the development of airway hyperresponsiveness remains unexplored.This experimental study human small bronchi aimed provide insight into which type 2 and 17 cytokines cause smooth muscle.Explanted isolated from lung tissue muscle cells were treated for 1 day(s), respectively, with 100 ng/mL IL-4, IL-5, IL-13, or IL-17A, contractile responses, Ca2+ mobilization, receptor expression...
Activation of taste receptors (TAS2Rs) by bitter agonists has been reported to cause bronchodilation. The aim this study was extend the information on effects responses induced different contractile mediators in a standard airway physiology preparation. Isometric were assessed guinea pig trachea (GPT). TAS2R administered either segments precontracted with for contraction or given before challenge stimuli, including antigen tissues from ovalbumin-sensitized animals. mRNA expression GPT...
Lung cancer is a leading cause of cancer-related death worldwide. Despite recent advances in tissue immunology, little known about the spatial distribution tissue-resident lymphocyte subsets lung tumors. Using high-parameter flow cytometry, we identified an accumulation lymphocytes including NK (trNK) cells and CD8+ memory T (TRM) toward center human non-small cell carcinomas (NSCLC). Chemokine receptor expression patterns indicated different modes tumor-infiltration and/or residency between...
Excessive uncontrolled airway narrowing is the main cause of symptoms in asthma, yet reasons behind this problem are still elusive. As mechanistic studies isolated airways from asthmatic individuals almost impossible to perform, aim study was investigate contractile responses intralobular bronchi (ILB) a guinea asthma model. These distal surrounded by parenchymal tissue and resemble functional characteristics human bronchi. Isolated ILB were mounted myographs measure smooth muscle reactions....
The clinical importance of prostaglandins and leukotrienes in asthma is well recognized; however, the biochemical role other lipid mediators (often termed oxylipins) regulation airway tone inflammation remains unclear. We therefore developed a workflow to investigate oxylipin physiology pharmacology two vitro models, intact human bronchus guinea pig trachea. Airways were isolated smooth muscle contraction was measured an organ bath following stimulation with either anti-IgE or ovalbumin....
Background: Epithelial cytokines, including IL-33 and Thymic stromal lymphopoietin (TSLP), have attracted interest because of their roles in chronic allergic inflammation-related conditions such as asthma. Mast cells are one the major targets IL-33, to which they respond by secreting cytokines. Most studies performed thus far investigated acute effects on mast cells. In current study, we how vs. prolonged exposure TSLP affects mediator synthesis IgE-mediated activation. Methods: Human lung...
The guinea pig trachea (GPT) is commonly used in airway pharmacology. aim of this study was to define the expression and function EP receptors for PGE(2) GPT as there has been ambiguity concerning their role.Expression mRNA key enzymes pathway were assessed by real-time PCR using species-specific primers. Functional studies performed tissue organ baths.Expression four found smooth muscle. displayed a bell-shaped concentration-response curve, where initial contraction inhibited EP(1) receptor...
Background: Mast cells are tissue-resident inflammatory defined by their high granularity and surface expression of the high-affinity IgE receptor, FcεRI, CD117/KIT, receptor for stem cell factor (SCF). There is a considerable heterogeneity among mast cells, both phenotypically functionally. Human generally divided into two main subtypes based on protease content; mucosa-associated MCT (tryptase positive chymase negative cell) connective tissue associated-residing MCTC cell). lung exhibit in...
Background Immunohistochemical analysis of granule-associated proteases has revealed that human lung mast cells constitute a heterogeneous population cells, with distinct subpopulations identified. However, systematic and comprehensive cell-surface markers to study cell heterogeneity yet be performed. Methods Human were obtained from lobectomies, the expression 332 was analyzed using flow cytometry LEGENDScreen™ kit. Markers exhibited high variance selected for additional analyses reveal...
Oxylipins are a class of low-abundance lipids formed via oxygenation fatty acids. These compounds include potent signaling molecules (e.g., octadecanoids, eicosanoids) that can exert essential functions in the pathophysiology inflammatory diseases including asthma. While some oxylipin cascades have been unraveled using LC-MS/MS-based methods, measurements homogenate samples do not represent spatial heterogeneity lipid metabolism. Mass spectrometry imaging (MSI) directly detects analytes from...
SUCNR1 is a sensor of extracellular succinate, Krebs cycle intermediate generated in excess during oxidative stress and has been linked to metabolic regulation inflammation. While mast cells express SUCNR1, its role cell reactivity allergic conditions such as asthma remains be elucidated.Cord blood-derived human line LAD-2 challenged by ligands were analyzed for the activation mediator release. Effects on cell-dependent bronchoconstriction assessed guinea pig trachea isolated small bronchi...
Previous research has emphasized the importance of eosinophils in allergic asthma, while paying less attention to neutrophils. The known functionality neutrophils inflammatory process recently changed and knowledge about subsets neutrophils, as characterized by their expression CD16 CD62L, surfaced. Their specific roles asthma are still unknown.To study functional differences between characterizing impact individual on airway smooth muscle reactivity.The direct effect hyperresponsiveness was...
BackgroundClinical research supports that exercise-induced bronchoconstriction (EIB) is caused by hyperosmolar triggering of mast cells. The reaction can be mimicked inhalation mannitol, but it has paradoxically previously not been possible to replicate this mode action mannitol in isolated airways.ObjectiveWe sought establish an ex vivo model EIB human small bronchi.MethodsSmall bronchi (inner diameter, 0.5-2 mm) from macroscopically healthy lung tissue were obtained 48 patients and mounted...
During asthma exacerbations, increased airway inflammation may impair the effects of β<sub>2</sub>-adrenoceptor (β<sub>2</sub>AR) agonists. It is unclear whether this impairment prevented by inhaled glucocorticoids (GCs). We have investigated relaxation carbachol-contracted mouse tracheal segments to β<sub>2</sub>AR agonists formoterol, terbutaline, and salmeterol. The were pre-exposed for 4 days proinflammatory cytokines tumor necrosis factor α (100 ng/ml) interleukin-1β (10 with or without...
Oxylipins are a class of low abundant lipids formed via oxygenation fatty acids. These compounds include potent signaling molecules (e.g., octadecanoids, eicosanoids) that can exert essential functions in the pathophysiology inflammatory diseases including asthma. While some oxylipin cascades have been unraveled using LC-MS/MS-based methods, measurements homogenate samples do not represent spatial heterogeneity lipid metabolism. Mass spectrometry imaging (MSI) directly detects analytes from...
Mast cells are critically involved in IgE-mediated diseases, e.g., allergies and asthma. Human mast heterogeneous, from different anatomical sites have been shown to respond differently certain stimuli drugs. The origin of the is therefore importance when setting up a model system, human lung highly relevant study context We set out optimize protocol activation cells. were extracted tissue obtained patients undergoing pulmonary resection by enzyme digestion mechanical disruption followed...
Mast cells are tissue-resident playing major roles in homeostasis and disease conditions. Lung mast particularly important airway inflammatory diseases such as asthma. Human classically divided into the subsets MC T TC , where express cell protease tryptase addition chymase, carboxypeptidase A3 (CPA3) cathepsin G. Apart from disctintion of subsets, little is known about heterogeniety human lung a deep analysis their has previously not been performed. We therefore performed single RNA...
Mast cells are well known for their detrimental effects in allergies and asthma, Wnt signaling has recently been implicated asthma other airway diseases. However, it is not if or how Wnts affect human mast cells. Since expression elevated individuals with linked to a Th2 profile, we hypothesized that could be affected by the context of asthma. We therefore sought investigate role cell development activation. first examined 10 main receptors, Frizzled 1–10 (FZD1–10), found several FZDs...