دورية أكاديمية
Human ALPI deficiency causes inflammatory bowel disease and highlights a key mechanism of gut homeostasis
| العنوان: | Human ALPI deficiency causes inflammatory bowel disease and highlights a key mechanism of gut homeostasis |
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| المؤلفون: | Parlato, Marianna, Charbit-Henrion, Fabienne, Pan, Jie, Romano, Claudio, Duclaux-Loras, Rémi, Le Du, Marie-Helene, Warner, Neil, Francalanci, Paola, Bruneau, Julie, Bras, Marc, Zarhrate, Mohammed, Bègue, Bernadette, Guegan, Nicolas, Rakotobe, Sabine, Kapel, Nathalie, de Angelis, Paola, Griffiths, Anne M., Fiedler, Karoline, Crowley, Eileen, Ruemmele, Frank, Muise, Aleixo M., Cerf-Bensussan, Nadine |
| المساهمون: | Laboratory of Intestinal Immunity (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), GENIUS Group, Service de Gastroentérologie, d'hépatologie et nutrition pédiatrique CHU Necker, Hôpital Necker - Enfants Malades AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The Hospital for sick children Toronto (SickKids), University of Messina, Department of Pathology, University of Alabama at Birmingham Birmingham (UAB), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), IRCCS Ospedale Pediatrico Bambino Gesù = Bambino Gesù Children’s Hospital, Université Paris Descartes - Paris 5 (UPD5), Service de pathologie CHU Necker, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Necker - Enfants Malades AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Plateforme de bioinformatique (UNIV Paris Descartes), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Toronto, Université Sorbonne Paris Cité (USPC), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010) |
| المصدر: | ISSN: 1757-4676. |
| بيانات النشر: | HAL CCSD Wiley Open Access |
| سنة النشر: | 2018 |
| المجموعة: | HAL-CEA (Commissariat à l'énergie atomique et aux énergies alternatives) |
| مصطلحات موضوعية: | INTGEN, B3S, inflammatory bowel diseases, intestinal phosphatase alkaline, monogenic disease, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Herein, we report the first identification of biallelic-inherited mutations inALPIas a Mendelian cause of inflammatory bowel disease in two unrelated patients.ALPIencodes for intestinal phosphatase alkaline, a brush border metalloenzyme that hydrolyses phosphate from the lipid A moiety of lipopolysaccharides and thereby drastically reduces Toll-like receptor 4 agonist activity. Prediction tools and structural modelling indicate that all mutations affect critical residues or inter-subunit interactions, and heterologous expression in HEK293T cells demonstrated that allALPImutations were loss of function.ALPImutations impaired either stability or catalytic activity of ALPI and rendered it unable to detoxify lipopolysaccharide-dependent signalling. Furthermore, ALPI expression was reduced in patients' biopsies, and ALPI activity was undetectable in ALPI-deficient patient's stool. Our findings highlight the crucial role of ALPI in regulating host-microbiota interactions and restraining host inflammatory responses. These results indicate thatALPImutations should be included in screening for monogenic causes of inflammatory bowel diseases and lay the groundwork for ALPI-based treatments in intestinal inflammatory disorders. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/29567797; hal-02183255; https://hal.science/hal-02183255Test; PUBMED: 29567797; PUBMEDCENTRAL: PMC5887907 |
| DOI: | 10.15252/emmm.201708483 |
| الإتاحة: | https://doi.org/10.15252/emmm.201708483Test https://hal.science/hal-02183255Test |
| رقم الانضمام: | edsbas.9F8D70A2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.15252/emmm.201708483 |
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