Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis
Summary: 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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720309645 |
| _version_ | 1828827347175866368 |
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| author | Berna Kaya Cristian Doñas Philipp Wuggenig Oscar E. Diaz Rodrigo A. Morales Hassan Melhem Pedro P. Hernández Tanay Kaymak Srustidhar Das Petr Hruz Yannick Franc Florian Geier C. Korcan Ayata Eduardo J. Villablanca Jan Hendrik Niess |
| author_facet | Berna Kaya Cristian Doñas Philipp Wuggenig Oscar E. Diaz Rodrigo A. Morales Hassan Melhem Pedro P. Hernández Tanay Kaymak Srustidhar Das Petr Hruz Yannick Franc Florian Geier C. Korcan Ayata Eduardo J. Villablanca Jan Hendrik Niess |
| author_sort | Berna Kaya |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-12T14:57:39Z |
| format | Article |
| id | doaj.art-ca646a69ee7447feb30e4ca230437f50 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T14:57:39Z |
| publishDate | 2020-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-ca646a69ee7447feb30e4ca230437f502022-12-22T00:20:52ZengElsevierCell Reports2211-12472020-08-01325107979Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal HomeostasisBerna Kaya0Cristian Doñas1Philipp Wuggenig2Oscar E. Diaz3Rodrigo A. Morales4Hassan Melhem5Pedro P. Hernández6Tanay Kaymak7Srustidhar Das8Petr Hruz9Yannick Franc10Florian Geier11C. Korcan Ayata12Eduardo J. Villablanca13Jan Hendrik Niess14Department of Biomedicine, University of Basel, 4031 Basel, SwitzerlandDivision of Immunology and Allergy, Department of Medicine, Solna, Karolinska Institutet and University Hospital, 17176 Stockholm, Sweden; Center for Molecular Medicine (CMM), 17176 Stockholm, SwedenDepartment of Biomedicine, University of Basel, 4031 Basel, SwitzerlandDivision of Immunology and Allergy, Department of Medicine, Solna, Karolinska Institutet and University Hospital, 17176 Stockholm, Sweden; Center for Molecular Medicine (CMM), 17176 Stockholm, SwedenDivision of Immunology and Allergy, Department of Medicine, Solna, Karolinska Institutet and University Hospital, 17176 Stockholm, Sweden; Center for Molecular Medicine (CMM), 17176 Stockholm, SwedenDepartment of Biomedicine, University of Basel, 4031 Basel, SwitzerlandInstitut Curie, PSL Research University, INSERM U934/CNRS UMR3215, Development and Homeostasis of Mucosal Tissues Group, 75005 Paris, FranceDepartment of Biomedicine, University of Basel, 4031 Basel, SwitzerlandDivision of Immunology and Allergy, Department of Medicine, Solna, Karolinska Institutet and University Hospital, 17176 Stockholm, Sweden; Center for Molecular Medicine (CMM), 17176 Stockholm, SwedenUniversity Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital of Basel, 4031 Basel, SwitzerlandCenter for Primary Care and Public Health (Unisanté), University of Lausanne, 1011 Lausanne, SwitzerlandDepartment of Biomedicine, University of Basel, 4031 Basel, Switzerland; Swiss Institute of Bioinformatics, 4031 Basel, SwitzerlandDepartment of Biomedicine, University of Basel, 4031 Basel, SwitzerlandDivision of Immunology and Allergy, Department of Medicine, Solna, Karolinska Institutet and University Hospital, 17176 Stockholm, Sweden; Center for Molecular Medicine (CMM), 17176 Stockholm, Sweden; Corresponding authorDepartment of Biomedicine, University of Basel, 4031 Basel, Switzerland; University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital of Basel, 4031 Basel, Switzerland; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720309645GPR35lysophosphatidic acidmacrophagescolitiszebrafishintestine |
| spellingShingle | Berna Kaya Cristian Doñas Philipp Wuggenig Oscar E. Diaz Rodrigo A. Morales Hassan Melhem Pedro P. Hernández Tanay Kaymak Srustidhar Das Petr Hruz Yannick Franc Florian Geier C. Korcan Ayata Eduardo J. Villablanca Jan Hendrik Niess Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis Cell Reports GPR35 lysophosphatidic acid macrophages colitis zebrafish intestine |
| title | Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis |
| title_full | Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis |
| title_fullStr | Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis |
| title_full_unstemmed | Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis |
| title_short | Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis |
| title_sort | lysophosphatidic acid mediated gpr35 signaling in cx3cr1 macrophages regulates intestinal homeostasis |
| topic | GPR35 lysophosphatidic acid macrophages colitis zebrafish intestine |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720309645 |
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