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https://www.readbyqxmd.com/read/29908086/innate-immune-response-reflects-disease-activity-in-eosinophilic-granulomatosis-with-polyangiitis
#1
Naomi Tsurikisawa, Chiyako Oshikata, Maiko Watanabe, Takahiro Tsuburai, Takeshi Kaneko, Hiroshi Saito
BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease characterized by allergic granulomatosis, necrotizing vasculitis, and peripheral blood eosinophilia. Interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and type-2 innate lymphoid cells (ILC2) are involved in the innate and type-2 immune responses in EGPA. However, the relationships among these molecules and the mechanisms underlying the development of EGPA remain unknown. OBJECTIVE: We investigated the relationships among peripheral blood eosinophil count, serum IL-33 and TSLP concentration, and peripheral blood ILC2 count in patients with EGPA, chronic eosinophilic pneumonia (CEP), or bronchial asthma (BA)...
June 16, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29907870/synergistic-activation-of-pro-inflammatory-type-2-cd8-t-lymphocytes-by-lipid-mediators-in-severe-eosinophilic-asthma
#2
Bart Hilvering, Timothy S C Hinks, Linda Stöger, Emanuele Marchi, Maryam Salimi, Rahul Shrimanker, Wei Liu, Wentao Chen, Jian Luo, Simei Go, Timothy Powell, Jennifer Cane, Samantha Thulborn, Ayako Kurioka, Tianqi Leng, Jamie Matthews, Clare Connolly, Catherine Borg, Mona Bafadhel, Christian B Willberg, Adaikalavan Ramasamy, Ratko Djukanović, Graham Ogg, Ian D Pavord, Paul Klenerman, Luzheng Xue
Human type-2 CD8+ T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia-a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+ CRTH2+ (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2 (PGD2 ) and cysteinyl leukotriene E4 (LTE4 ) are also increased in the airways of the same group of patients...
June 15, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29867934/exposure-of-intestinal-epithelial-cells-to-short-and-long-chain-fructo-oligosaccharides-and-cpg-oligodeoxynucleotides-enhances-peanut-specific-t-helper-1-polarization
#3
Simone M Hayen, Henny G Otten, Saskia A Overbeek, André C Knulst, Johan Garssen, Linette E M Willemsen
Background: Non-digestible oligosaccharides promote colonization of beneficial gut bacteria and have direct immunomodulatory effects. Apical exposure of intestinal epithelial cells (IECs) to short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) in a transwell co-culture model enhanced the CpG-induced (TLR-9 ligand) T helper 1 (Th1) phenotype and regulatory IL-10 response of underlying peripheral mononuclear cells (PBMCs) of healthy donors. scGOS is derived from lactose and may pose risks in severe cow's milk allergic patients, and scFOS/lcFOS may be an alternative...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29848886/association-of-the-polymorphisms-in-th2-chemotaxis-related-genes-with-the-development-and-prognosis-of-autoimmune-thyroid-diseases
#4
Naoki Omori, Mikio Watanabe, Naoya Inoue, Junpei Taniguchi, Yoh Hidaka, Yoshinori Iwatani
The prognosis of autoimmune thyroid disease (AITD) is difficult to predict. Th2 cells suppress the differentiation of Th1 and Th17 cells, which are associated with the prognosis of AITD. However, there are few reports as to whether Th2 chemotaxis-related genes, such as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), IL-25, TARC/CCL17 (Thymus and activation regulated chemokine/chemokine ligand 17) or STAT6 (Signal transducer and activator of transcription 6), affect the pathology of and/or susceptibility to AITD...
May 30, 2018: Endocrine Journal
https://www.readbyqxmd.com/read/29842945/circulating-integrin-alpha4-beta7-lymphocytes-targeted-by-vedolizumab-have-a-pro-inflammatory-phenotype
#5
James D Lord, S Alice Long, Donna M Shows, Jerill Thorpe, Katherine Schwedhelm, Janice Chen, Mariko Kita, Jane H Buckner
Integrin alpha4/beta7 on circulating lymphocytes identifies them as gut-tropic, and can be targeted by the humanized antibody vedolizumab to treat inflammatory bowel disease (IBD). We found lymphocytes expressing alpha4/beta7 were significantly more responsive to the pro-inflammatory cytokines IL-6, IL-7, and IL-21, and less responsive to the regulatory T cell (Treg)-supporting cytokine IL-2. Alpha4/beta7 was expressed by a smaller percent of FOXP3 + Helios+ thymically-derived Tregs (tTregs) than FOXP3 + Helios- peripherally-derived Tregs (pTregs) or FOXP3- effector T cells...
May 26, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29765200/efficacy-and-safety-of-the-crth2-antagonist-azd1981-as-add-on-therapy-to-inhaled-corticosteroids-and-long-acting-%C3%AE-2-agonists-in-patients-with-atopic-asthma
#6
Eric D Bateman, Christopher O'Brien, Paul Rugman, Sally Luke, Stefan Ivanov, Mohib Uddin
Objectives: To evaluate the efficacy and safety of AZD1981, a potent, specific antagonist of the CRTh2 receptor, as add-on therapy to inhaled corticosteroids (ICS) and long-acting β2 -agonists (LABA), in patients with persistent asthma with an allergic component. Patients and methods: In this placebo-controlled, parallel-group Phase IIb study, patients with persistent atopic asthma on ICS and LABA were randomized to receive 12 weeks of treatment with placebo or AZD1981 (80 mg daily, 200 mg daily, and 10 mg, 40 mg, 100 mg, or 400 mg twice daily [BID])...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29743346/pgd2-dp2-receptor-activation-promotes-severe-viral-bronchiolitis-by-suppressing-ifn-%C3%AE-production
#7
Rhiannon B Werder, Jason P Lynch, Jennifer C Simpson, Vivian Zhang, Nick H Hodge, Matthew Poh, Elizabeth Forbes-Blom, Christina Kulis, Mark L Smythe, John W Upham, Kirsten Spann, Mark L Everard, Simon Phipps
Prostaglandin D2 (PGD2) signals through PGD2 receptor 2 (DP2, also known as CRTH2) on type 2 effector cells to promote asthma pathogenesis; however, little is known about its role during respiratory syncytial virus (RSV) bronchiolitis, a major risk factor for asthma development. We show that RSV infection up-regulated hematopoietic prostaglandin D synthase expression and increased PGD2 release by cultured human primary airway epithelial cells (AECs). Moreover, PGD2 production was elevated in nasopharyngeal samples from young infants hospitalized with RSV bronchiolitis compared to healthy controls...
May 9, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29678990/chemoattractant-receptor-homologous-molecule-expressed-on-th2-cells-crth2-antagonists-in-asthma-a-systematic-review-and-meta-analysis-protocol
#8
Wei Liu, Jie Min, Hongli Jiang, Bing Mao
INTRODUCTION: More than 20 orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists have moved forward to clinical development in recent years for the treatment of asthma. However, evidence from individual randomised controlled trials (RCTs) has demonstrated inconsistent results in their efficacy and safety. METHODS AND ANALYSIS: PubMed/Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, Global Index Medicus, Cochrane Central Register of Controlled Trials and Scopus will be searched from inception to 30 December 2017 for eligible RCTs, with additional studies being identified by manual searches...
April 20, 2018: BMJ Open
https://www.readbyqxmd.com/read/29607536/dp1-receptor-signaling-prevents-the-onset-of-intrinsic-apoptosis-in-eosinophils-and-functions-as-a-transcriptional-modulator
#9
Miriam Peinhaupt, David Roula, Anna Theiler, Miriam Sedej, Rudolf Schicho, Gunther Marsche, Eva M Sturm, Ian Sabroe, Marc E Rothenberg, Akos Heinemann
Prostaglandin (PG) D2 is the ligand for the G-protein coupled receptors DP1 (D-type prostanoid receptor 1) and DP2 (also known as chemoattractant receptor homologous molecule, expressed on Th2 cells; CRTH2). Both, DP1 and DP2 are expressed on the cellular surface of eosinophils; although it has become quite clear that PGD2 induces eosinophil migration mainly via DP2 receptors, the role of DP1 in eosinophil responses has remained elusive. In this study, we addressed how DP1 receptor signaling complements the pro-inflammatory effects of DP2...
April 1, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29517573/usefulness-of-basophil-activation-tests-for-diagnosis-of-sugammadex-induced-anaphylaxis
#10
Tatsuo Horiuchi, Akihiko Yokohama, Masaki Orihara, Yukinari Tomita, Akihiro Tomioka, Nagahide Yoshida, Kenichiro Takahashi, Shigeru Saito, Tomonori Takazawa
BACKGROUND: Sugammadex is used to reverse the effects of neuromuscular blocking agents in many cases of general anesthesia. However, there are several reports of anaphylaxis after its use. Skin testing is the gold standard for detecting the causative agent of anaphylaxis. However, due to the lack of validated protocols for skin testing with sugammadex, the diagnostic accuracy might be inadequate. Recently, the basophil activation test (BAT) has been established as a tool to detect the causative agent of anaphylaxis with high sensitivity and specificity...
May 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29454096/jak-stat-inhibitors-and-other-small-molecule-cytokine-antagonists-for-the-treatment-of-allergic-disease
#11
REVIEW
Michael D Howell, Carolyn Fitzsimons, Paul A Smith
OBJECTIVE: To provide an overview of janus kinase (JAK), chemoattractant receptor homologous molecule expressed on TH 2 cells (CRTH2), and phosphodiesterase 4 (PDE4) inhibitors in allergic disorders. DATA SOURCES: PubMed literature review. STUDY SELECTIONS: Articles included in this review discuss the emerging mechanism of action of small molecule inhibitors and their use in the treatment of atopic dermatitis (AD), asthma, and allergic rhinitis (AR)...
April 2018: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29449864/seasonal-variation-in-circulating-group-2-innate-lymphoid-cells-in-mugwort-allergic-asthmatics-during-and-outside-pollen-season
#12
Qing Miao, Yan Wang, Yong-Ge Liu, Yi-Xin Ren, Hui Guan, Zhen Li, Wei Xu, Li Xiang
Background: Group 2 innate lymphoid cells (ILC2s) are a newly identified cell population with the potent capability to produce Th2-type cytokines in a non-antigen specific manner. Previous study demonstrated that enhanced circulating ILC2s in cat-allergic patient after experimental allergen challenge, whereas the effects of natural allergen exposure on peripheral ILC2s are still unclear. We therefore examined the variations in circulating ILC2s among asthmatic patients sensitized to different allergens in- and outside- pollen season...
2018: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/29427987/advances-and-evolving-concepts-in-allergic-asthma
#13
Hui-Ying Tung, Evan Li, Cameron Landers, An Nguyen, Farrah Kheradmand, J Morgan Knight, David B Corry
Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis...
February 2018: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29363343/fevipiprant-in-the-treatment-of-asthma
#14
REVIEW
Christobelle White, Adam Wright, Christopher Brightling
Asthma is common and in many, particularly those with more severe disease, there remains a substantial unmet need. Success with biologics targeting eosinophilic inflammation underscore the value of treating inflammation in asthma beyond corticosteroids. Fevipiprant (QAW039) is an oral treatment for asthma. It competitively and reversibly antagonises the prostaglandin D2 receptor 2 (DP2) expressed on inflammatory and structural cells. Areas covered: We reviewed fevipiprant's mode of action and efficacy against other current and emerging pharmacological interventions for moderate-to-severe asthma...
February 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29335338/crth2-promotes-endoplasmic-reticulum-stress-induced-cardiomyocyte-apoptosis-through-m-calpain
#15
Shengkai Zuo, Deping Kong, Chenyao Wang, Jiao Liu, Yuanyang Wang, Qiangyou Wan, Shuai Yan, Jian Zhang, Juan Tang, Qianqian Zhang, Luheng Lyu, Xin Li, Zhixin Shan, Li Qian, Yujun Shen, Ying Yu
Apoptotic death of cardiac myocytes is associated with ischemic heart disease and chemotherapy-induced cardiomyopathy. Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) is highly expressed in the heart. However, its specific role in ischemic cardiomyopathy is not fully understood. Here, we demonstrated that CRTH2 disruption markedly improved cardiac recovery in mice postmyocardial infarction and doxorubicin challenge by suppressing cardiomyocyte apoptosis. Mechanistically, CRTH2 activation specifically facilitated endoplasmic reticulum (ER) stress-induced cardiomyocyte apoptosis via caspase-12-dependent pathway...
January 15, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29296700/il-33-il-25-and-tslp-induce-a-distinct-phenotypic-and-activation-profile-in-human-type-2-innate-lymphoid-cells
#16
Ana Camelo, Guglielmo Rosignoli, Yoichiro Ohne, Ross A Stewart, Catherine Overed-Sayer, Matthew A Sleeman, Richard D May
Innate lymphoid cells (ILCs) represent a distinct branch of the lymphoid lineage composed of 3 major subpopulations: ILC1, ILC2, and ILC3. ILCs are mainly described as tissue-resident cells but can be detected at low levels in human blood. However, unlike mouse ILCs, there is still no consistent methodology to purify and culture these cells that enables in-depth analysis of their intrinsic biology. Here, we describe defined culture conditions for ILC2s, which allowed us to dissect the roles of interleukin 2 (IL-2), IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) individually, or in combination, in modulating ILC2 phenotype and function...
April 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29276415/crth2-antagonists-in-asthma-current-perspectives
#17
REVIEW
Dave Singh, Arjun Ravi, Thomas Southworth
Chemoattractant receptor-homologous molecule expressed on TH 2 cells (CRTH2) binds to prostaglandin D2 . CRTH2 is expressed on various cell types including eosinophils, mast cells, and basophils. CRTH2 and prostaglandin D2 are involved in allergic inflammation and eosinophil activation. Orally administered CRTH2 antagonists are in clinical development for the treatment of asthma. The biology and clinical trial data indicate that CRTH2 antagonists should be targeted toward eosinophilic asthma. This article reviews the clinical evidence for CRTH2 involvement in asthma pathophysiology and clinical trials of CRTH2 antagonists in asthma...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29110986/the-synthesis-of-2-3-6-trisubstituted-1-oxo-1-2-dihydroisoquinolines-as-potent-crth-2-antagonists
#18
Xianhai Huang, Ashwin Rao, Wei Zhou, Robert Aslanian, Ravi Nargund, Alexei Buevich, Li-Kang Zhang, Hongchen Qiu, Xiaoxin Yang, Charles G Garlisi, Craig Correll, Anandan Palani
New synthetic methods were developed for the preparation of 2,3,6-trisubstituted 1-oxo-1,2-dihydroisoquinolines as CRTh2 antagonists. The isoquinolinone core could be constructed before the introduction of substitution groups or synthesized through a catalytic intramolecular cyclization reaction with desired substitution groups properly installed. These synthetic strategies have helped to accelerate the SAR development of this series, and potent lead compounds were identified in both the CRTh2 receptor binding assay and the CD11b biomarker assay...
December 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28964637/neuroendocrine-cells-derived-chemokine-vasoactive-intestinal-polypeptide-vip-in-allergic-diseases
#19
REVIEW
Alok K Verma, Murli Manohar, Sathisha Upparahalli Venkateshaiah, Anil Mishra
Worldwide increase incidences of allergic diseases have heightened the interest of clinicians and researchers to understand the role of neuroendocrine cells in the recruitment and activation of inflammatory cells. Several pieces of evidence revealed the association of neuropeptides in the pathogenesis of allergic diseases. Importantly, one such peptide that is secreted by neuronal cells and immune cells exerts a wide spectrum of immunological functions as cytokine/chemokine is termed as Vasoactive Intestinal Peptide (VIP)...
December 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28928446/tumour-derived-pgd2-and-nkp30-b7h6-engagement-drives-an-immunosuppressive-ilc2-mdsc-axis
#20
Sara Trabanelli, Mathieu F Chevalier, Amaia Martinez-Usatorre, Alejandra Gomez-Cadena, Bérengère Salomé, Mariangela Lecciso, Valentina Salvestrini, Grégory Verdeil, Julien Racle, Cristina Papayannidis, Hideaki Morita, Irene Pizzitola, Camille Grandclément, Perrine Bohner, Elena Bruni, Mukul Girotra, Rani Pallavi, Paolo Falvo, Elisabeth Oppliger Leibundgut, Gabriela M Baerlocher, Carmelo Carlo-Stella, Daniela Taurino, Armando Santoro, Orietta Spinelli, Alessandro Rambaldi, Emanuela Giarin, Giuseppe Basso, Cristina Tresoldi, Fabio Ciceri, David Gfeller, Cezmi A Akdis, Luca Mazzarella, Saverio Minucci, Pier Giuseppe Pelicci, Emanuela Marcenaro, Andrew N J McKenzie, Dominique Vanhecke, George Coukos, Domenico Mavilio, Antonio Curti, Laurent Derré, Camilla Jandus
Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored...
September 19, 2017: Nature Communications
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