14 results on '"Van Dyken S"'
Search Results
2. 940 ILC2s and Type 2 immunity influence hair follicle stem cell proliferation and skin homeostasis
- Author
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Ricardo-Gonzalez, R., primary, Van Dyken, S., additional, and Locksley, R., additional
- Published
- 2018
- Full Text
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3. LB973 Characterization of tissue-resident ILC2 heterogeneity in homeostasis
- Author
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Ricardo-Gonzalez, R., primary, Van Dyken, S., additional, Molofsky, A., additional, Nussbaum, J., additional, Lee, J., additional, and Locksley, R., additional
- Published
- 2017
- Full Text
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4. Group 2 innate lymphoid cells utilize the IRF4-IL-9 module to coordinate epithelial cell maintenance of lung homeostasis
- Author
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Mohapatra, A, primary, Van Dyken, S J, additional, Schneider, C, additional, Nussbaum, J C, additional, Liang, H-E, additional, and Locksley, R M, additional
- Published
- 2016
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5. T-cell activation results in microheterogeneous changes in glycosylation of CD45
- Author
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Hernandez, J. D., primary, Klein, J., additional, Van Dyken, S. J., additional, Marth, J. D., additional, and Baum, L. G., additional
- Published
- 2007
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6. Ozone Exposure Enhances Endotoxin-Induced Mucous Cell Metaplasia in Rat Pulmonary Airways
- Author
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Wagner, J. G., primary, Van Dyken, S. J., additional, Wierenga, J. R., additional, Hotchkiss, J. A., additional, and Harkema, J. R., additional
- Published
- 2003
- Full Text
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7. Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase.
- Author
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Díaz RE, Ecker AK, Correy GJ, Asthana P, Young ID, Faust B, Thompson MC, Seiple IB, Van Dyken S, Locksley RM, and Fraser JS
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- Animals, Hydrogen-Ion Concentration, Mice, Protein Conformation, Crystallography, X-Ray, Protein Binding, Ligands, Kinetics, Acetylglucosamine metabolism, Acetylglucosamine chemistry, Models, Molecular, Chitinases metabolism, Chitinases chemistry, Molecular Dynamics Simulation, Chitin metabolism, Chitin chemistry
- Abstract
Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian Chitinase (AMCase), is an enzyme known for its ability to function under acidic conditions in the stomach but is also active in tissues with more neutral pHs, such as the lung. Here, we used a combination of biochemical, structural, and computational modeling approaches to examine how the mouse homolog (mAMCase) can act in both acidic and neutral environments. We measured kinetic properties of mAMCase activity across a broad pH range, quantifying its unusual dual activity optima at pH 2 and 7. We also solved high-resolution crystal structures of mAMCase in complex with oligomeric GlcNAcn, the building block of chitin, where we identified extensive conformational ligand heterogeneity. Leveraging these data, we conducted molecular dynamics simulations that suggest how a key catalytic residue could be protonated via distinct mechanisms in each of the two environmental pH ranges. These results integrate structural, biochemical, and computational approaches to deliver a more complete understanding of the catalytic mechanism governing mAMCase activity at different pH. Engineering proteins with tunable pH optima may provide new opportunities to develop improved enzyme variants, including AMCase, for therapeutic purposes in chitin degradation., Competing Interests: RD, AE, GC, PA, IY, BF, MT, IS No competing interests declared, SV, RL S.J.V.D. and R.M.L. are listed as inventors on a patent United States application: 17/505,561 for the use of chitinases to treat fibrotic lung disease. S.J.V.D., R.M.L., and J.S.F. are listed as inventors on a patent for mutant chitinases with enhanced expression and activity, JF S.J.V.D. and R.M.L. are listed as inventors on a patent for the use of chitinases to treat fibrotic lung disease. United States application: 17/505,561 S.J.V.D., R.M.L., and J.S.F. are listed as inventors on a patent for mutant chitinases with enhanced expression and activity, (© 2023, Díaz et al.)
- Published
- 2024
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8. Sensory neurons promote immune homeostasis in the lung.
- Author
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Tamari M, Del Bel KL, Ver Heul AM, Zamidar L, Orimo K, Hoshi M, Trier AM, Yano H, Yang TL, Biggs CM, Motomura K, Shibuya R, Yu CD, Xie Z, Iriki H, Wang Z, Auyeung K, Damle G, Demircioglu D, Gregory JK, Hasson D, Dai J, Chang RB, Morita H, Matsumoto K, Jain S, Van Dyken S, Milner JD, Bogunovic D, Hu H, Artis D, Turvey SE, and Kim BS
- Subjects
- Animals, Humans, Mice, Cytokines, Inflammation, Lymphocytes, Dermatitis, Atopic immunology, Immunity, Innate, Lung immunology, Sensory Receptor Cells enzymology
- Abstract
Cytokines employ downstream Janus kinases (JAKs) to promote chronic inflammatory diseases. JAK1-dependent type 2 cytokines drive allergic inflammation, and patients with JAK1 gain-of-function (GoF) variants develop atopic dermatitis (AD) and asthma. To explore tissue-specific functions, we inserted a human JAK1 GoF variant (JAK1
GoF ) into mice and observed the development of spontaneous AD-like skin disease but unexpected resistance to lung inflammation when JAK1GoF expression was restricted to the stroma. We identified a previously unrecognized role for JAK1 in vagal sensory neurons in suppressing airway inflammation. Additionally, expression of Calcb/CGRPβ was dependent on JAK1 in the vagus nerve, and CGRPβ suppressed group 2 innate lymphoid cell function and allergic airway inflammation. Our findings reveal evolutionarily conserved but distinct functions of JAK1 in sensory neurons across tissues. This biology raises the possibility that therapeutic JAK inhibitors may be further optimized for tissue-specific efficacy to enhance precision medicine in the future., Competing Interests: Declaration of interests B.S.K. is founder of KliRNA Biotech; he has served as a consultant for 23andMe, ABRAX Japan, AbbVie, Almirall, Amgen, Arcutis Biotherapeutics, Arena Pharmaceuticals, argenx, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Clexio Biosciences, Eli Lilly and Company, Escient Pharmaceuticals, Evommune, Galderma, Genentech, GlaxoSmithKline, Granular Therapeutics, Incyte Corporation, Innovaderm Research, Janssen, Kiniksa, LEO Pharma, Maruho, Novartis, Pfizer, Recens Medical, Regeneron Pharmaceuticals, Sanofi, Septerna, Triveni Bio, Vial, and WebMD; he has stock in ABRAX Japan, KliRNA Biotech, Locus Biosciences, and Recens Medical; he holds a patent for the use of JAK1 inhibitors for chronic pruritus; and he has a patent pending for the use of JAK inhibitors for interstitial cystitis. D.A. has contributed to scientific advisory boards at Pfizer, Takeda, FARE, and the KRF. D.B. is the founder of Lab11 Therapeutics.., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
- Full Text
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9. A role for IL-33-activated ILC2s in eosinophilic vasculitis.
- Author
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Kotas ME, Dion J, Van Dyken S, Ricardo-Gonzalez RR, Danel CJ, Taillé C, Mouthon L, Locksley RM, and Terrier B
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- Animals, Autoimmunity immunology, Disease Models, Animal, Humans, Immunity, Innate immunology, Lung metabolism, Lung pathology, Mice, Churg-Strauss Syndrome immunology, Churg-Strauss Syndrome metabolism, Churg-Strauss Syndrome pathology, Interleukin-33 immunology, Interleukin-33 metabolism, Lymphocytes immunology, Lymphocytes metabolism
- Abstract
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease with poorly understood mechanisms. Here, we report that patients with EGPA have elevated levels of TSLP, IL-25, and soluble ST2, which are well-characterized cytokine "alarmins" that activate or modulate type 2 innate lymphoid cells (ILC2s). Patients with active EGPA have a concurrent reduction in circulating ILC2s, suggesting a role for ILC2s in the pathogenesis of this disease. To explore the mechanism of these findings in patients, we established a model of EGPA in which active vasculitis and pulmonary hemorrhage were induced by IL-33 administration in predisposed, hypereosinophilic mice. In this model, induction of pulmonary hemorrhage and vasculitis was dependent on ILC2s and signaling through IL4Rα. In the absence of IL4Rα or STAT6, IL-33-treated mice had less vascular leak and pulmonary edema, less endothelial activation, and reduced eotaxin production, cumulatively leading to a reduction of pathologic eosinophil migration into the lung parenchyma. These results offer a mouse model for use in future mechanistic studies of EGPA, and they suggest that IL-33, ILC2s, and IL4Rα signaling may be potential targets for further study and therapeutic targeting in patients with EGPA.
- Published
- 2021
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10. Ly6c Lo non-classical monocytes promote resolution of rhesus rotavirus-mediated perinatal hepatic inflammation.
- Author
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Alkhani A, Levy CS, Tsui M, Rosenberg KA, Polovina K, Mattis AN, Mack M, Van Dyken S, Wang BM, Maher JJ, and Nijagal A
- Subjects
- Animals, Hepatitis, Animal pathology, Mice, Mice, Inbred BALB C, Mice, Knockout, Monocytes pathology, Rotavirus Infections pathology, Antigens, Ly immunology, Hepatitis, Animal immunology, Monocytes immunology, Rotavirus immunology, Rotavirus Infections immunology
- Abstract
Perinatal hepatic inflammation can have devastating consequences. Monocytes play an important role in the initiation and resolution of inflammation, and their diverse functions can be attributed to specific cellular subsets: pro-inflammatory or classical monocytes (Ly6c
Hi ) and pro-reparative or non-classical monocytes (Ly6cLo ). We hypothesized that inherent differences in Ly6cHi classical monocytes and Ly6cLo non-classical monocytes determine susceptibility to perinatal hepatic inflammation in late gestation fetuses and neonates. We found an anti-inflammatory transcriptional profile expressed by Ly6cLo non-classical monocytes, and a physiologic abundance of these cells in the late gestation fetal liver. Unlike neonatal pups, late gestation fetuses proved to be resistant to rhesus rotavirus (RRV) mediated liver inflammation. Furthermore, neonatal pups were rendered resistant to RRV-mediated liver injury when Ly6cLo non-classical monocytes were expanded. Pharmacologic inhibition of Ly6cLo non-classical monocytes in this setting restored susceptibility to RRV-mediated disease. These data demonstrate that Ly6cLo monocytes promote resolution of perinatal liver inflammation in the late gestation fetus, where there is a physiologic expansion of non-classical monocytes, and in the neonatal liver upon experimental expansion of these cells. Therapeutic strategies directed towards enhancing Ly6cLo non-classical monocyte function may mitigate the detrimental effects of perinatal liver inflammation.- Published
- 2020
- Full Text
- View/download PDF
11. Pulmonary neuroendocrine cells amplify allergic asthma responses.
- Author
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Sui P, Wiesner DL, Xu J, Zhang Y, Lee J, Van Dyken S, Lashua A, Yu C, Klein BS, Locksley RM, Deutsch G, and Sun X
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors deficiency, Basic Helix-Loop-Helix Transcription Factors genetics, Calcitonin Gene-Related Peptide metabolism, Cytokines biosynthesis, Disease Models, Animal, Epithelial Cells immunology, Epithelial Cells pathology, Female, Goblet Cells pathology, Humans, Hyperplasia, Mice, gamma-Aminobutyric Acid biosynthesis, gamma-Aminobutyric Acid metabolism, Asthma immunology, Asthma pathology, Lung pathology, Neuroendocrine Cells immunology, Neuroendocrine Cells pathology
- Abstract
Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells whose function is poorly understood. Here we show that Ascl1 -mutant mice that have no PNECs exhibit severely blunted mucosal type 2 response in models of allergic asthma. PNECs reside in close proximity to group 2 innate lymphoid cells (ILC2s) near airway branch points. PNECs act through calcitonin gene-related peptide (CGRP) to stimulate ILC2s and elicit downstream immune responses. In addition, PNECs act through the neurotransmitter γ-aminobutyric acid (GABA) to induce goblet cell hyperplasia. The instillation of a mixture of CGRP and GABA in Ascl1 -mutant airways restores both immune and goblet cell responses. In accordance, lungs from human asthmatics show increased PNECs. These findings demonstrate that the PNEC-ILC2 neuroimmunological modules function at airway branch points to amplify allergic asthma responses., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2018
- Full Text
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12. Sialylation regulates peripheral tolerance in CD4+ T cells.
- Author
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Brennan PJ, Saouaf SJ, Van Dyken S, Marth JD, Li B, Bhandoola A, and Greene MI
- Subjects
- Animals, Autoantibodies immunology, Autoantibodies metabolism, CD4-Positive T-Lymphocytes metabolism, Flow Cytometry, Immunoprecipitation, Mice, Mice, Inbred CBA, Mice, Knockout, Mice, Transgenic, Neuraminidase metabolism, Neuraminidase pharmacology, Phosphotyrosine immunology, Phosphotyrosine metabolism, Thy-1 Antigens immunology, Thy-1 Antigens metabolism, Vibrio cholerae enzymology, CD4-Positive T-Lymphocytes immunology, Immune Tolerance physiology, Neuraminidase immunology
- Abstract
Decreased binding by the 6C10 auto-antibody serves as a unique marker for CD4+ T cell unresponsiveness after the induction of T cell tolerance in Vbeta8.1 TCR transgenic mice. We further define the nature of the epitope recognized by the 6C10 antibody to be a subset of Thy-1 bearing incompletely sialylated N-linked glycans, and furthermore, we demonstrate that tolerant CD4+ T cells have an increased degree of cell-surface sialylation. To test the significance of the altered glycosylation state identified by the 6C10 auto-antibody in the tolerant CD4+ T cell population, surface sialic acid was cleaved enzymatically. Treatment of purified peripheral CD4+ T cells with Vibrio cholerae sialidase (VCS) leads to increased 6C10 binding, significantly enhances proliferation in the tolerant CD4+ population and corrects defects in phosphotyrosine signaling observed in the tolerant CD4+ T cell. Furthermore, in vivo administration of VCS enhances proliferation in both tolerant and naive CD4+ T cell subsets. These studies suggest that sialylation of glycoproteins on the surface of the CD4+ T cell contributes to the regulation of T cell responsiveness in the tolerant state.
- Published
- 2006
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13. The eicosanoid, 15-(S)-HETE, stimulates secretion of mucin-like glycoprotein by the corneal epithelium.
- Author
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Jackson RS 2nd, Van Dyken SJ, McCartney MD, and Ubels JL
- Subjects
- Animals, Biological Transport, Epithelium, Corneal metabolism, Epithelium, Corneal ultrastructure, Fluoresceins pharmacokinetics, Rabbits, Epithelium, Corneal drug effects, Eye Proteins metabolism, Hydroxyeicosatetraenoic Acids pharmacology, Mucins metabolism
- Abstract
Purpose: The eicosanoid, 15-(S)-hydroxyeicosa-5Z, 8Z-11Z, 13E-tetraenoic acid (15-(S)-HETE), is known to stimulate production of mucin glycoprotein by airway epithelium. This study investigated the effect of 15-(S)-HETE on the mucin glycoprotein secretion by the corneal epithelium., Methods: To determine the effect of dose, corneas of anesthetized New Zealand White rabbits were treated with 50, 500, or 5,000 nM 15-(S)-HETE in artificial tears for 120 minutes. To determine the time to onset of the response, corneas were treated with 500 or 1,000 nM 15-(S)-HETE in balanced salt solution for periods ranging from 5 to 120 minutes. Corneas were fixed for electron microscopy in fixative containing 0.5% cetylpyridinium chloride (CPC) to stabilize the layer of mucin-like glycoprotein on the corneal surface. The mucin layer thickness was measured by image analysis of electron micrographs., Results: The layer of CPC-fixed mucin-like glycoprotein on the surface of control corneas was 0.46 +/- 0.04 microm thick. After treatment with 15-(S)-HETE, the thickness of the mucin layer increased to 0.64 +/- 0.1 microm at 50 or 5,000 nM HETE and as much as 1.02 +/- 0.2 microm in response to 500 nM HETE. Mucin thickness reached a statistical maximum of 0.59 +/- 0.1 microm after only 5 minutes of exposure to 500 or 1,000 nM HETE., Conclusions: Exposure of the cornea to 15-(S)-HETE causes a rapid-onset increase in the thickness of a layer of mucin-like glycoprotein on the surface of the corneal epithelium. This supports previous reports that corneal epithelial cells produce mucin and suggests that treatment with topical 15-(S)-HETE may be effective in treating ocular surface mucin deficiency in dry eye syndrome.
- Published
- 2001
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14. Endotoxin enhancement of ozone-induced mucous cell metaplasia is neutrophil-dependent in rat nasal epithelium.
- Author
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Wagner JG, Van Dyken SJ, Hotchkiss JA, and Harkema JR
- Subjects
- Air Pollutants toxicity, Animals, Drug Interactions, Immune Sera pharmacology, Inhalation Exposure, Male, Metaplasia chemically induced, Metaplasia pathology, Mucins biosynthesis, Mucins genetics, Nasal Mucosa metabolism, Nasal Mucosa pathology, Neutropenia chemically induced, Neutrophil Infiltration immunology, Neutrophils drug effects, RNA, Messenger metabolism, Rats, Rats, Inbred F344, Turbinates drug effects, Turbinates pathology, Lipopolysaccharides pharmacology, Nasal Mucosa drug effects, Neutrophil Infiltration drug effects, Neutrophils immunology, Ozone toxicity, Pseudomonas aeruginosa
- Abstract
Ozone, the primary oxidant gas in photochemical smog, causes neutrophilic inflammation and mucous cell metaplasia (MCM) in the nasal transitional epithelium (NTE) of rats and monkeys. Bacterial endotoxin is another common airborne agent that induces acute neutrophilic inflammation, but not MCM, in NTE. It does, however, enhance ozone-induced MCM in rat nasal airways (Fanucchi et al., 1998, Toxicol. Appl. Pharmacol. 152, 1-9). In the present study, F344 rats exposed to filtered air or 0.5 ppm ozone (8 h/day for 3 days) were intranasally instilled with sterile saline or 100 microg endotoxin 24 h and 48 h after the third ozone exposure. To determine the role of neutrophilic inflammation in endotoxin-induced potentiation of the MCM caused by ozone, half of the rats were depleted of circulating neutrophils prior to saline or endotoxin instillations. Rats were killed 6 h or 3 days after the last intranasal instillation, and nasal tissues were processed for (1) light microscopy and morphometric analysis to determine the number of infiltrating neutrophils and the volume amount (density) of stored mucosubstances in the NTE, and (2) quantitative RT-PCR analysis of steady-state mucin gene (rMuc-5AC) mRNA levels in the NTE. Endotoxin induced a transient influx of neutrophils in both air- and ozone-exposed rats that was completely blocked by neutrophil depletion. Endotoxin increased rMuc-5AC mRNA levels in the NTE of ozone-exposed rats. Neutrophil depletion, however, had no effect on endotoxin-induced upregulation of mucin gene mRNA levels. Endotoxin enhanced the ozone-induced increase in stored mucosubstances (4-fold increase), but only in neutrophil-sufficient rats. These data indicate that endotoxin enhancement of ozone-induced upregulation of rMuc-5AC mRNA levels is neutrophil-independent, while its effects on intraepithelial production and storage of mucus glycoproteins is dependent on the presence of neutrophils.
- Published
- 2001
- Full Text
- View/download PDF
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