A5008993441- Dermatology and Skin Diseases
- Psoriasis: Treatment and Pathogenesis
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Cutaneous lymphoproliferative disorders research
- T-cell and B-cell Immunology
- T-cell and Retrovirus Studies
- Plant biochemistry and biosynthesis
- Bioactive Natural Diterpenoids Research
- Urticaria and Related Conditions
- Neuroinflammation and Neurodegeneration Mechanisms
- Whipple's Disease and Interleukins
- Lymphoma Diagnosis and Treatment
- Microscopic Colitis
- Nail Diseases and Treatments
- Allergic Rhinitis and Sensitization
- Neuropeptides and Animal Physiology
- Fungal Infections and Studies
- Tryptophan and brain disorders
- Stress Responses and Cortisol
- Food Allergy and Anaphylaxis Research
- Cancer Mechanisms and Therapy
- Gut microbiota and health
Leo Pharma (Denmark)
2014-2023
Leo Pharma (Australia)
2015
University of Copenhagen
2003-2009
Institute of Molecular Biology
2006
Canadian Society of Intestinal Research
2001
McMaster University
1999
Via cytoplasmic signal transduction pathways, cytokines induce a variety of biological responses and modulate the outcome inflammatory diseases malignancies. Crohn's disease is chronic bowel unknown etiology. Perturbation intestinal cytokine homeostasis believed to play pivotal role, but pathogenesis not fully understood. Here, we study T cells from healthy volunteers. We show that STAT3 STAT4 are constitutively activated in patients The activation specific, because other STAT proteins...
The chronic skin inflammation psoriasis is crucially dependent on the IL-23/IL-17 cytokine axis. Although IL-23 expressed by psoriatic keratinocytes and immune cells, only cell-derived believed to be disease relevant. Here we use a genetic mouse model show that keratinocyte-produced sufficient cause with an IL-17 profile. Furthermore, reveal cell-autonomous nuclear function for actin polymerizing molecule N-WASP, which controls expression in regulating degradation of histone...
Patients with atopic dermatitis harbor deficiencies in subsets of NK cells that can be therapeutically reversed to improve disease mice.
Abstract Substances that penetrate the skin surface can act as allergens and induce a T cell–mediated inflammatory disease called contact hypersensitivity (CHS). IL-17 is key cytokine in CHS was originally thought to be produced solely by CD4+ cells. However, it now known several cell types, including γδ cells, produce IL-17. In this study, we determine role of especially dendritic epidermal cells (DETCs), CHS. Using well-established model for which 2,4-dinitrofluorobenzene (DNFB) used...
Atopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. In this study, we used microarray analysis to investigate differences gene expression lesional from patients mild extrinsic or intrinsic AD compared healthy controls psoriasis skin. The primary aim was identify differentially expressed genes involved barrier formation inflammation, compare our results those reported for moderate severe AD. contrast AD, of the...
Psoriasis vulgaris is characterised by epidermal hyper-proliferation and infiltration of immune cells including dendritic (DCs) T cells. The inflammation driven a complex interplay between skin involving interleukin (IL)-17A, IL-23 TNF-α as key drivers. calcipotriol/betamethasone dipropionate two-compound fixed combination product widely used for topical treatment psoriasis. However, the mechanism behind its high efficacy has not been elucidated in detail.Here, we investigated compared...
Itch is a common symptom that can greatly diminish quality of life. Histamine potent endogenous pruritogen, and while antihistamines are often the first-line treatment for itch, in conditions like chronic spontaneous urticaria (CSU), many patients remain symptomatic receiving maximal doses. Mechanisms drive resistance to poorly defined.
Coevolutionary theory suggests that an arms race between plants and herbivores yields increased plant specialized metabolite diversity the geographic mosaic of coevolution predicts coevolutionary interactions vary across scales. Consequently, is expected to be highest in hotspots, regions, which exhibit strong reciprocal selection on interacting species. Despite being well established theoretical frameworks, technical limitations have precluded rigorous hypothesis testing. Here we aim at...
The interleukin (IL)-23/IL-17 immune axis is of central importance in psoriasis. However, the impact IL-17 family cytokines other than IL-17A psoriasis has not been fully established.To elucidate contribution psoriasis.To address expression and localization cytokines, lesional nonlesional skin samples from patients with were analysed by several complementary methods, including quantitative polymerase chain reaction, immunoassays, situ hybridization immunohistochemistry. Mechanistic studies...
Herein, we report the discovery of a series JAK1-selective kinase inhibitors with high potency and excellent JAK family subtype selectivity. A fragment screening hit 1 pyrazolopyridone core JAK1 bias was selected as starting point for our fragment-based lead generation efforts. two-stage strategy chosen dual aims improving selectivity: Optimization lipophilic ribose pocket-targeting substituent followed by introduction variety P-loop-targeting functional groups. Combining best moieties from...
Crohn's disease is an idiopathic inflammatory condition. However, little known about the changes that occur in muscularis externa, despite fact this tissue contributes to motility and stricture formation. We characterized immune activity externa from intestinal segments of patients evaluated role IL-4 -13 as well signal transducer activator transcription (STAT)6 contractility cultured human smooth muscle cells. CD3+ve cells (P < 0.01) protein were significantly increased compared with...
Abstract Skin models mimicking features of psoriasis‐related inflammation are needed to support the development new drugs in dermatology. Reconstructed skin lack tissue complexity, including a fully competent barrier, and presence and/or diversity immune cells. Here, we describe InflammaSkin®, novel human Th17‐driven ex vivo model. In this model, skin‐resident T cells situ activated by intradermal injection anti‐CD3 anti‐CD28 antibodies Th17 cell polarization is sustained culture chemically...
Interleukin-4 (IL-4) plays a pivotal role in the induction and maintenance of allergy by promoting Th2 differentiation B cell isotype switching to IgE. Studies on STAT6-deficient mice have demonstrated essential STAT6 mediating biological functions IL-4. IL-4 induces tyrosine phosphorylation STAT6, which turn leads transcription IL-4-specific genes. In addition, serine has recently been reported. Here we study functional kinases phosphatases involved. We show that inhibition protein...
Purpose: To examine the effect of human retinal pigment epithelial (RPE) cells on phytohemagglutinin (PHA) activation T cells. Methods: Resting peripheral blood lymphocytes (PBLs) were stimulated with PHA or without presence γ -irradiated RPE Proliferation and cell cycle profile thereafter investigated by 3H-thymidine incorporation flow cytometric analysis. In addition, PBLs expression CD69, major histocompatibility complex (MHC) class I II, CD3, as well IL-2 receptor chains evaluated...
Intestinal inflammation due to nematode infection impairs enteric cholinergic nerve function and induces hypercontractility of intestinal muscle. Macrophages have been implicated in the neural changes, but subpopulation mechanism involved are unknown. We examined whether macrophages alter nerves by virtue their ability activate lymphocytes via major histocompatibility complex (MHC) II-restricted antigen presentation. also attempted evaluate role macrophage subsets using op/op mice deficient...