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https://www.readbyqxmd.com/read/28433687/steroid-resistance-of-airway-type-2-innate-lymphoid-cells-ilc2s-from-severe-asthma-the-role-of-thymic-stromal-cell-lymphopoietin-tslp
#1
Sucai Liu, Mukesh Verma, Lidia Michalec, Weimin Liu, Anand Sripada, Donald Rollins, James Good, Yoko Ito, HongWei Chu, Magdalena M Gorska, Richard J Martin, Rafeul Alam
BACKGROUND: ILC2s represent an important type 2 immune cell. Glucocorticoid regulation of human ILC2s is largely unknown. OBJECTIVE: To assess steroid resistance of human blood and airway ILC2s from asthmatic patients and examine its mechanism of induction. METHODS: We studied human blood and lung ILC2s from asthmatic and control subjects by flow cytometry and ELISA. RESULTS: Dexamethasone (Dex) inhibited (P=0.04) CRTH2 and type 2 cytokine expression by blood ILC2s stimulated with IL25 and IL33...
April 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28422515/allergen-induced-increases-in-sputum-levels-of-group-2-innate-lymphoid-cells-in-asthmatic-subjects
#2
Ruchong Chen, Steven G Smith, Brittany Salter, Amani El-Gammal, John Paul Oliveria, Caitlin Obminski, Rick Watson, Paul M O'Byrne, Gail M Gauvreau, Roma Sehmi
RATIONALE: Group 2 innate lymphoid cells (ILC2), a major source of type 2 cytokines, initiate eosinophilic inflammatory responses in murine models of asthma. OBJECTIVES: Investigate the role of ILC2 in allergen-induced airway eosinophilic responses in atopic asthmatics. METHODS: Using a diluent-controlled allergen challenge cross-over study, where all subjects (n=10) developed allergen-induced early and late responses , airway eosinophilia and increased methacholine airway responsiveness, bone marrow, blood and sputum samples were collected pre- and post-inhalation challenge...
April 19, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28394950/generation-and-characterization-of-an-antagonistic-monoclonal-antibody-against-an-extracellular-domain-of-mouse-dp2-crth2-gpr44-receptors-for-prostaglandin-d2
#3
Nanae Nagata, Hiroko Iwanari, Hidetoshi Kumagai, Osamu Kusano-Arai, Yuichi Ikeda, Kosuke Aritake, Takao Hamakubo, Yoshihiro Urade
Prostaglandin D2 (PGD2) is a lipid mediator involved in sleep regulation and inflammation. PGD2 interacts with 2 types of G protein-coupled receptors, DP1 and DP2/CRTH2 (chemoattractant receptor homologous molecule expressed on T helper type 2 cells)/GPR44 to show a variety of biological effects. DP1 activation leads to Gs-mediated elevation of the intracellular cAMP level, whereas activation of DP2 decreases this level via the Gi pathway; and it also induces G protein-independent, arrestin-mediated cellular responses...
2017: PloS One
https://www.readbyqxmd.com/read/28392807/efficacy-and-safety-of-setipiprant-in-seasonal-allergic-rhinitis-results-from-phase-2-and-phase-3-randomized-double-blind-placebo-and-active-referenced-studies
#4
Paul Ratner, Charles P Andrews, Frank C Hampel, Bruce Martin, Dale E Mohar, Denis Bourrelly, Parisa Danaietash, Sara Mangialaio, Jasper Dingemanse, Abdel Hmissi, Jay van Bavel
BACKGROUND: Antagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks. METHODS: A Phase 2 trial and a Phase 3 trial were conducted at seven centers in Texas, USA during the Mountain Cedar pollen season...
2017: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/28303135/a-human-lin-cd123-cd127-low-population-endowed-with-ilc-features-and-migratory-capabilities-contributes-to-immunopathological-hallmarks-of-psoriasis
#5
Luz María Mora-Velandia, Octavio Castro-Escamilla, Andrés González Méndez, Cristina Aguilar-Flores, Martha Velázquez-Avila, María Isabel Tussié-Luna, Juan Téllez-Sosa, César Maldonado-García, Fermín Jurado-Santacruz, Eduardo Ferat-Osorio, Jesus Martínez-Barnetche, Rosana Pelayo, Laura C Bonifaz
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127(-) ILC populations and an early ILC precursor (EILP) CD127(low). ILC development has predominately been investigated in mouse models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28299574/physiological-and-pathological-roles-of-15-deoxy-%C3%AE-12-14-prostaglandin-j2-in-the-central-nervous-system-and-neurological-diseases
#6
REVIEW
Tatsurou Yagami, Yasuhiro Yamamoto, Hiromi Koma
Prostaglandins (PGs) are divided into conventional PGs, e.g., PGD2, and cyclopentenone-type PGs, e.g., 15-deoxy-Δ(12,14) prostaglandin J2 (15d-PGJ2). PGD2 is non-enzymatically metabolized to PGJ2, Δ(12)-PGJ2, and 15d-PGJ2. In the central nervous system, 15d-PGJ2 differentiates embryonic midbrain cells into dopaminergic neuronal cells via its nuclear peroxysome proliferator-activated receptor-γ (PPARγ). 15d-PGJ2 exerts conflict actions: proinflammatory and anti-inflammatory activities. In the brain, 15d-PGJ2 possesses opposite functions as a neuroprotectant at low concentrations and a neurotoxicant at high concentrations in the brain...
March 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28222358/tyrosine-kinase-inhibition-is-an-important-factor-for-gene-expression-of-crth2-in-human-eosinophils-and-lymphocytes-a-novel-mechanism-for-explaining-eosinophils-recruitment-by-the-neuro-immune-axis-in-allergic-rhinitis
#7
A E El-Shazly, P Roncarati, M Lejeune, P P Lefebvre, P Delvenne
We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However, there are neither studies on the CRTH2 gene expression in allergic rhinitis (AR) nor in the effect of tyrosine kinase inhibitors in CRTH2 gene regulation. Our Objectives were to study the gene expression modulation of CRTH2 receptor in AR patients and the effect of tyrosine kinase inhibitors (TKIs) on CRTH2 gene modulation...
February 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28194801/differences-in-eosinophil-molecular-profiles-between-children-and-adults-with-eosinophilic-esophagitis
#8
Christine Lingblom, Timo Käppi, Henrik Bergquist, Mogens Bove, Rikard Arkel, Robert Saalman, Christine Wennerås
BACKGROUND: Eosinophilic esophagitis (EoE) afflicts both children and adults. It has been debated whether pediatric and adult EoE represent different disease entities. The objectives of this study were to determine if the blood eosinophil molecular pattern of children with EoE is: 1) distinct from that of healthy children; and 2) different from that of adults with EoE. METHODS: Blood eosinophils from children and adults with EoE, and healthy controls, were analyzed with flow cytometry regarding levels of CD23, CD44, CD54, CRTH2, FOXP3 and galectin-10...
February 14, 2017: Allergy
https://www.readbyqxmd.com/read/28106273/the-immunoglobulin-superfamily-member-cd200r-identifies-cells-involved-in-type-2-immune-responses
#9
Lars H Blom, Britta C Martel, Lau F Larsen, Camilla V Hansen, Malene P Christensen, Nanna Juel-Berg, Thomas Litman, Lars K Poulsen
BACKGROUND: The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim of this investigation was to identify surface markers associated with type 2 inflammation. METHODS: Naïve human CD4(+) T-cells were short-term activated in the presence or absence of IL-4, and analysed for expression of >300 cell-surface proteins...
January 20, 2017: Allergy
https://www.readbyqxmd.com/read/28099820/new-and-developing-non-adrenoreceptor-small-molecule-drugs-for-the-treatment-of-asthma
#10
REVIEW
Neil C Thomson
Inhaled corticosteroids (ICS) alone or in combination with an inhaled long-acting beta2-agonist (LABA) are the preferred long-term treatment for adults and adolescents with symptomatic asthma. Additional drugs include leukotriene-receptor antagonists, slow-release theophylline and the long-acting muscarinic antagonist (LAMA) tiotropium (approved in 2015). There is a need for more effective therapies, as many patients continue to have poorly controlled asthma. Areas covered: New and developing long-acting non-adrenoreceptor synthetic drugs for the treatment of symptomatic chronic asthma despite treatment with an ICS alone or combined with a LABA...
February 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28035475/increased-baff-expression-in-nasal-polyps-is-associated-with-local-ige-production-th2-response-and-concomitant-asthma
#11
Dilidaer, Yan Zheng, Zhuofu Liu, Xianting Hu, Jia Zhang, Li Hu, Miaomiao Han, Dehui Wang, Huabin Li
B-cell activating factor of the TNF family is critical for the survival and maturation of B cells and play a role in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP). In this study, nasal tissues were enrolled from 25 CRSwNP patients (asthmatic, 16; non-asthmatic, 9), 12 CRSsNP patients and ten control subjects, respectively. The immunoreactivity of BAFF, CD20 and CD138 were examined using immunohistochemistry staining. The mRNA expression of BAFF, CD20, εGLT, AID, GATA3 and CRTH2 were examined using real-time RT-PCR...
December 29, 2016: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/27872865/cxcr3-ccr5-and-crth2-chemokine-receptor-expression-in-lymphocytes-infiltrating-thyroid-nodules-with-coincident-hashimoto-s-thyroiditis-obtained-by-fine-needle-aspiration-biopsy
#12
Jan Jiskra, Marie Antošová, Jan Krátký, Hana Vítková, Zdeňka Límanová, Helena Marečková, Eliška Potluková
Objective. To determine the expression of chemokine receptors in lymphocytes from thyroid nodules and peripheral blood in patients with and without Hashimoto's thyroiditis (HT). Patients and Methods. The study included 46 women with thyroid nodules and HT and 60 women with thyroid nodules without HT (controls) who underwent a fine needle aspiration biopsy (FNAB). Expression of chemokine receptors CXCR3, CCR5, and CRTH2 was assessed by flow cytometry in lymphocytes from FNAB samples and from peripheral blood...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27773851/intradermal-grass-pollen-immunotherapy-increases-th2-and-ige-responses-and-worsens-respiratory-allergic-symptoms
#13
Anna Slovick, Abdel Douiri, Rachel Muir, Andrea Guerra, Konstantinos Tsioulos, Evie Hay, Emily P S Lam, Joanna Kelly, Janet L Peacock, Sun Ying, Mohamed H Shamji, David J Cousins, Stephen R Durham, Stephen J Till
BACKGROUND: Repeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy. OBJECTIVE: We sought to evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis. METHODS: We randomly assigned 93 adults with grass pollen-induced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control...
October 20, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27735066/anti-inflammatory-therapies-in-atopic-dermatitis
#14
REVIEW
A Heratizadeh, T Werfel
The pathogenesis of atopic dermatitis (AD) is multifactorial and complex. Consequently, clinical signs and symptoms vary strongly depending on individually relevant trigger factors and the stage of the disease. So far, treatment of AD was commonly limited to topical treatment or, in more severe cases, to systemic drugs mostly approved for other indications than AD. However, emerging data on new anti-inflammatory agents have been published in the recent years. As these new substances specifically focus on immune responses in AD, these are partially considered as possible 'breakthrough' in the treatment of AD...
December 2016: Allergy
https://www.readbyqxmd.com/read/27699264/depletion-of-major-pathogenic-cells-in-asthma-by-targeting-crth2
#15
Tao Huang, Meredith Hazen, Yonglei Shang, Meijuan Zhou, Xiumin Wu, Donghong Yan, Zhonghua Lin, Margaret Solon, Elizabeth Luis, Hai Ngu, Yongchang Shi, Arna Katewa, David F Choy, Nandhini Ramamoorthi, Erick R Castellanos, Mercedesz Balazs, Min Xu, Wyne P Lee, Marissa L Matsumoto, Jian Payandeh, Joseph R Arron, Jo-Anne Hongo, Jianyong Wang, Isidro Hötzel, Cary D Austin, Karin Reif
Eosinophilic inflammation and Th2 cytokine production are central to the pathogenesis of asthma. Agents that target either eosinophils or single Th2 cytokines have shown benefits in subsets of biomarker-positive patients. More broadly effective treatment or disease-modifying effects may be achieved by eliminating more than one inflammatory stimulator. Here we present a strategy to concomitantly deplete Th2 T cells, eosinophils, basophils, and type-2 innate lymphoid cells (ILC2s) by generating monoclonal antibodies with enhanced effector function (19A2) that target CRTh2 present on all 4 cell types...
May 19, 2016: JCI Insight
https://www.readbyqxmd.com/read/27621597/two-phase-ii-randomized-trials-on-the-crth2-antagonist-azd1981-in-adults-with-asthma
#16
RANDOMIZED CONTROLLED TRIAL
Piotr Kuna, Leif Bjermer, Göran Tornling
BACKGROUND: Chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cell (CRTh2) receptor antagonists is being investigated for asthma. OBJECTIVES: The aim of this study was to assess the effects of the CRTh2 receptor antagonist, AZD1981 (with/without inhaled corticosteroids [ICSs]), on lung function and asthma control. PATIENTS AND METHODS: Adults aged 18-60 years were enrolled in two randomized, placebo-controlled, parallel-group trials (protocol number: D9830C00003 [study 1, n=209] and protocol number: D9830C00004 [study 2, n=510])...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27581546/effect-of-memory-cd4-t-cells-signal-transducer-and-activator-of-transcription-stats-functional-shift-on-cytokine-releasing-properties-in-asthma
#17
Zhihong Chen, Jue Pan, Yi Jia, Dandan Li, Zhihui Min, Xiaoqiong Su, Honglei Yuan, Geng Shen, Shengxuan Cao, Lei Zhu, Xiangdong Wang
BACKGROUND: Recent data have demonstrated that long-lived memory T cells are present in the human lung and can play significant roles in the pathogenesis of specific allergic and autoimmune diseases. However, most evidence has been obtained from mouse studies, and the potential roles of memory T cells in human allergic diseases, such as asthma, remain largely unknown. METHODS: Thirty-three asthmatics, 26 chronic obstructive pulmonary disease (COPD) patients, and 22 healthy volunteers were enrolled in this study...
February 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27558866/an-s-warfarin-and-azd1981-interaction-in-vitro-and-clinical-pilot-data-suggest-the-n-deacetylated-amino-acid-metabolite-as-the-primary-perpetrator
#18
Ken Grime, Rikard Pehrson, Pär Nordell, Michael Gillen, Wolfgang Kühn, Timothy Mant, Marie Brännström, Petter Svanberg, Barry Jones, Clive Brealey
AIM: AZD1981 is an orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) receptor antagonist progressed to phase II trials for the treatment of allergic asthma. Previously performed in vitro human hepatocyte incubations identified N-deacetylated AZD1981 as a primary metabolite. We report on metabolite exposure from a clinical excretion balance, on in vitro studies performed to determine the likelihood of a metabolite-dependent drug-drug interaction (DDI) and on a clinical warfarin DDI study...
February 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27531793/-dendritic-cells-promote-the-proliferation-of-peripheral-blood-crth2-cells-cd4-cd294-th2-and-help-b-cells-to-secrete-immunoglobulin
#19
Fa-Qing Tian, Juan Li, Ju-Heng Li, Mei-Qin Tang, Xiao-Hui Cheng, Ying-Cai Huang, Hui-Qing Li
Objective:To investigate the promotive effect of dendritic cells(DCs) on proliferation of CRTH2 (CD4(+)CD294(+)Th2) cells and the influence of CRTH2 cells on secretion of immunoglobulin from B cells so as to provide a new approach for amplification and sorting of Th2 cells. Methods:DCs were induced from peripheral blood mononuclear cells, then the loaded-BCGV-Ag-DCs were cocultured with T cells, and the mixed lymphocyte reaction(MLR) was performed by CCK8 method. The phenotypes of DCs and CRTH2 cells were detected by flow cytometry...
August 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27525671/assessing-the-new-and-emerging-treatments-for-atopic-dermatitis
#20
Lawrence F Eichenfield, Sheila F Friedlander, Eric L Simpson, Alan D Irvine
The newer and emerging treatments for atopic dermatitis (AD) focus on blockade of inflammatory cytokines, especially those that derive from T helper cell type 2 (TH2) and are associated with a pathway of immunoglobulin E (IgE) sensitization. Among the proinflammatory cytokines that have been identified as promising therapeutic targets are chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2), IgE, thymic stromal lymphopoietin (TSLP), and several monoclonal antibodies that block key cytokine pathways in the innate immune response...
June 2016: Seminars in Cutaneous Medicine and Surgery
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