دورية أكاديمية
Siglec-8 antibody reduces eosinophils and mast cells in a transgenic mouse model of eosinophilic gastroenteritis.
| العنوان: | Siglec-8 antibody reduces eosinophils and mast cells in a transgenic mouse model of eosinophilic gastroenteritis. |
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| المؤلفون: | Youngblood BA; Allakos, Inc., Redwood City, California, USA., Brock EC; Allakos, Inc., Redwood City, California, USA., Leung J; Allakos, Inc., Redwood City, California, USA., Falahati R; Allakos, Inc., Redwood City, California, USA., Bochner BS; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Rasmussen HS; Allakos, Inc., Redwood City, California, USA., Peterson K; Division of Gastroenterology, Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA., Bebbington C; Allakos, Inc., Redwood City, California, USA., Tomasevic N; Allakos, Inc., Redwood City, California, USA. |
| المصدر: | JCI insight [JCI Insight] 2019 Oct 03; Vol. 4 (19). Date of Electronic Publication: 2019 Oct 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Antibodies, Monoclonal/*pharmacology , Antigens, CD/*immunology , Antigens, Differentiation, B-Lymphocyte/*immunology , Enteritis/*drug therapy , Eosinophilia/*drug therapy , Eosinophils/*drug effects , Gastritis/*drug therapy , Lectins/*drug effects , Mast Cells/*immunology, Animals ; Disease Models, Animal ; Enteritis/immunology ; Eosinophilia/immunology ; Eosinophilic Esophagitis/drug therapy ; Eosinophils/immunology ; Female ; Gastritis/immunology ; Gastroenteritis ; Humans ; Lectins/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Ovalbumin |
| مستخلص: | Aberrant accumulation and activation of eosinophils and potentially mast cells (MCs) contribute to the pathogenesis of eosinophilic gastrointestinal diseases (EGIDs), including eosinophilic esophagitis (EoE), gastritis (EG), and gastroenteritis (EGE). Current treatment options, such as diet restriction and corticosteroids, have limited efficacy and are often inappropriate for chronic use. One promising new approach is to deplete eosinophils and inhibit MCs with a monoclonal antibody (mAb) against sialic acid-binding immunoglobulin-like lectin 8 (Siglec-8), an inhibitory receptor selectively expressed on MCs and eosinophils. Here, we characterize MCs and eosinophils from human EG and EoE biopsies using flow cytometry and evaluate the effects of an anti-Siglec-8 mAb using a potentially novel Siglec-8-transgenic mouse model in which EG/EGE was induced by ovalbumin sensitization and intragastric challenge. MCs and eosinophils were significantly increased and activated in human EG and EoE biopsies compared with healthy controls. Similar observations were made in EG/EGE mice. In Siglec-8-transgenic mice, anti-Siglec-8 mAb administration significantly reduced eosinophils and MCs in the stomach, small intestine, and mesenteric lymph nodes and decreased levels of inflammatory mediators. In summary, these findings suggest a role for both MCs and eosinophils in EGID pathogenesis and support the evaluation of anti-Siglec-8 as a therapeutic approach that targets both eosinophils and MCs. |
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| فهرسة مساهمة: | Keywords: Allergy; Gastroenterology; Mast cells; Mouse models; Therapeutics |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Antigens, CD) 0 (Antigens, Differentiation, B-Lymphocyte) 0 (Lectins) 0 (SIGLEC8 protein, human) 9006-59-1 (Ovalbumin) |
| SCR Disease Name: | Eosinophilic enteropathy |
| تواريخ الأحداث: | Date Created: 20190830 Date Completed: 20201013 Latest Revision: 20201013 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC6795394 |
| DOI: | 10.1172/jci.insight.126219 |
| PMID: | 31465299 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2379-3708 |
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| DOI: | 10.1172/jci.insight.126219 |