Academic Journal
Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis
| العنوان: | Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis |
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| المؤلفون: | Kaya, Berna, Doñas, Cristian, Wuggenig, Philipp, Diaz, Oscar, E, Morales, Rodrigo, A, Melhem, Hassan, Hernández, Pedro, P, Kaymak, Tanay, Das, Srustidhar, Hruz, Petr, Franc, Yannick, Geier, Florian, Ayata, C. Korcan, Villablanca, Eduardo, J, Niess, Jan, Hendrik |
| المساهمون: | Génétique et Biologie du Développement, Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 2211-1247. |
| بيانات النشر: | HAL CCSD Elsevier Inc |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity |
| الوصف: | International audience ; Single-nucleotide polymorphisms in the gene encoding G protein-coupled receptor 35 (GPR35) are associated with increased risk of inflammatory bowel disease. However, the mechanisms by which GPR35 modulates intestinal immune homeostasis remain undefined. Here, integrating zebrafish and mouse experimental models, we demonstrate that intestinal Gpr35 expression is microbiota dependent and enhanced upon inflammation. Moreover, murine GPR35+ colonic macrophages are characterized by enhanced production of pro-inflammatory cytokines. We identify lysophosphatidic acid (LPA) as a potential endogenous ligand produced during intestinal inflammation, acting through GPR35 to induce tumor necrosis factor (Tnf) expression in macrophages. Mice lacking Gpr35 in CX3CR1+ macrophages aggravate colitis when exposed to dextran sodium sulfate, which is associated with decreased transcript levels of the corticosterone-generating gene Cyp11b1 and macrophage-derived Tnf. Administration of TNF in these mice restores Cyp11b1 expression and intestinal corticosterone production and ameliorates DSS-induced colitis. Our findings indicate that LPA signals through GPR35 in CX3CR1+ macrophages to maintain TNF-mediated intestinal homeostasis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | hal-03968569; https://hal.science/hal-03968569; https://hal.science/hal-03968569/document; https://hal.science/hal-03968569/file/mmc2.pdf |
| DOI: | 10.1016/j.celrep.2020.107979 |
| الاتاحة: | https://hal.science/hal-03968569 https://hal.science/hal-03968569/document https://hal.science/hal-03968569/file/mmc2.pdf https://doi.org/10.1016/j.celrep.2020.107979 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.F8882D35 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.celrep.2020.107979 |
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