دورية أكاديمية
Autoimmune receptor encephalitis in mice induced by active immunization with conformationally stabilized holoreceptors.
| العنوان: | Autoimmune receptor encephalitis in mice induced by active immunization with conformationally stabilized holoreceptors. |
|---|---|
| المؤلفون: | Jones BE; Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA., Tovar KR; Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA., Goehring A; Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA., Jalali-Yazdi F; Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA., Okada NJ; Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA., Gouaux E; Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA., Westbrook GL; Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. westbroo@ohsu.edu. |
| المصدر: | Science translational medicine [Sci Transl Med] 2019 Jul 10; Vol. 11 (500). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science |
| مواضيع طبية MeSH: | Encephalitis/*immunology , Hashimoto Disease/*immunology , Receptors, N-Methyl-D-Aspartate/*chemistry , Receptors, N-Methyl-D-Aspartate/*immunology , Vaccination/*adverse effects, Animals ; Autoantibodies/blood ; Autoantibodies/immunology ; B-Lymphocytes/immunology ; Behavior, Animal ; Brain/pathology ; Encephalitis/blood ; Encephalitis/pathology ; HEK293 Cells ; Hashimoto Disease/blood ; Hashimoto Disease/pathology ; Humans ; Immunoglobulin G/blood ; Inflammation/pathology ; Leukocytes/pathology ; Mice ; Neuroglia/metabolism ; Neurons/metabolism ; Protein Conformation ; Proteolipids/metabolism ; Rats ; T-Lymphocytes/immunology |
| مستخلص: | Autoimmunity to membrane proteins in the central nervous system has been increasingly recognized as a cause of neuropsychiatric disease. A key recent development was the discovery of autoantibodies to N -methyl-d-aspartate (NMDA) receptors in some cases of encephalitis, characterized by cognitive changes, memory loss, and seizures that could lead to long-term morbidity or mortality. Treatment approaches and experimental studies have largely focused on the pathogenic role of these autoantibodies. Passive antibody transfer to mice has provided useful insights but does not produce the full spectrum of the human disease. Here, we describe a de novo autoimmune mouse model of anti-NMDA receptor encephalitis. Active immunization of immunocompetent mice with conformationally stabilized, native-like NMDA receptors induced a fulminant encephalitis, consistent with the behavioral and pathologic characteristics of human cases. Our results provide evidence for neuroinflammation and immune cell infiltration as components of the autoimmune response in mice. Use of transgenic mice indicated that mature T cells and antibody-producing cells were required for disease induction. This active immunization model may provide insights into disease induction and a platform for testing therapeutic approaches. (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.) |
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| معلومات مُعتمدة: | R01 NS038631 United States NS NINDS NIH HHS; United States HHMI Howard Hughes Medical Institute; F32 MH115595 United States MH NIMH NIH HHS; R37 NS038631 United States NS NINDS NIH HHS; R01 NS080979 United States NS NINDS NIH HHS; P30 NS061800 United States NS NINDS NIH HHS |
| المشرفين على المادة: | 0 (Autoantibodies) 0 (Immunoglobulin G) 0 (Proteolipids) 0 (Receptors, N-Methyl-D-Aspartate) 0 (proteoliposomes) |
| SCR Disease Name: | Hashimoto's encephalitis |
| تواريخ الأحداث: | Date Created: 20190712 Date Completed: 20200724 Latest Revision: 20231013 |
| رمز التحديث: | 20231013 |
| مُعرف محوري في PubMed: | PMC6729143 |
| DOI: | 10.1126/scitranslmed.aaw0044 |
| PMID: | 31292262 |
| قاعدة البيانات: | MEDLINE |
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