دورية أكاديمية
Anti-commensal IgG Drives Intestinal Inflammation and Type 17 Immunity in Ulcerative Colitis.
| العنوان: | Anti-commensal IgG Drives Intestinal Inflammation and Type 17 Immunity in Ulcerative Colitis. |
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| المؤلفون: | Castro-Dopico, Tomas, Dennison, Thomas W, Ferdinand, John R, Mathews, Rebeccah J, Fleming, Aaron, Clift, Dean, Stewart, Benjamin J, Jing, Chenzhi, Strongili, Konstantina, Labzin, Larisa I, Monk, Edward JM, Saeb-Parsy, Kourosh, Bryant, Clare E, Clare, Simon, Parkes, Miles, Clatworthy, Menna R |
| بيانات النشر: | Elsevier BV //dx.doi.org/10.1016/j.immuni.2019.02.006 Immunity |
| سنة النشر: | 2019 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Fcγ receptors, IL-1β, IgG, inflammatory bowel disease, type 17 immunity, Animals, Antibodies, Bacterial, Colitis, Ulcerative, Dextran Sulfate, Gastrointestinal Microbiome, Gene Expression Regulation, Genotype, Humans, Immunoglobulin G, Inflammation, Interleukin-1beta, Interleukin-8, Intestinal Mucosa, Macrophages, Mice, Phagocytes, RNA, Messenger, Reactive Oxygen Species, Receptors, Th17 Cells |
| الوصف: | Inflammatory bowel disease is a chronic, relapsing condition with two subtypes, Crohn's disease (CD) and ulcerative colitis (UC). Genome-wide association studies (GWASs) in UC implicate a FCGR2A variant that alters the binding affinity of the antibody receptor it encodes, FcγRIIA, for immunoglobulin G (IgG). Here, we aimed to understand the mechanisms whereby changes in FcγRIIA affinity would affect inflammation in an IgA-dominated organ. We found a profound induction of anti-commensal IgG and a concomitant increase in activating FcγR signaling in the colonic mucosa of UC patients. Commensal-IgG immune complexes engaged gut-resident FcγR-expressing macrophages, inducing NLRP3- and reactive-oxygen-species-dependent production of interleukin-1β (IL-1β) and neutrophil-recruiting chemokines. These responses were modulated by the FCGR2A genotype. In vivo manipulation of macrophage FcγR signal strength in a mouse model of UC determined the magnitude of intestinal inflammation and IL-1β-dependent type 17 immunity. The identification of an important contribution of IgG-FcγR-dependent inflammation to UC has therapeutic implications. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; application/vnd.openxmlformats-officedocument.wordprocessingml.document; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/289634Test |
| DOI: | 10.17863/CAM.36883 |
| الإتاحة: | https://doi.org/10.17863/CAM.36883Test https://www.repository.cam.ac.uk/handle/1810/289634Test |
| رقم الانضمام: | edsbas.75D085EF |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.36883 |
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