Sterile triggers drive joint inflammation in TNF‐ and IL‐1β‐dependent mouse arthritis models
Abstract Arthritis is the most common extra‐intestinal complication in inflammatory bowel disease (IBD). Conversely, arthritis patients are at risk for developing IBD and often display subclinical gut inflammation. These observations suggest a shared disease etiology, commonly termed “the gut‐joint‐...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-10-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202317691 |
| _version_ | 1797280039457259520 |
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| author | Alexandra Thiran Ioanna Petta Gillian Blancke Marie Thorp Guillaume Planckaert Maude Jans Vanessa Andries Korneel Barbry Elisabeth Gilis Julie Coudenys Tino Hochepied Christian Vanhove Eric Gracey Emilie Dumas Teddy Manuelo Ivan Josipovic Geert vanLoo Dirk Elewaut Lars Vereecke |
| author_facet | Alexandra Thiran Ioanna Petta Gillian Blancke Marie Thorp Guillaume Planckaert Maude Jans Vanessa Andries Korneel Barbry Elisabeth Gilis Julie Coudenys Tino Hochepied Christian Vanhove Eric Gracey Emilie Dumas Teddy Manuelo Ivan Josipovic Geert vanLoo Dirk Elewaut Lars Vereecke |
| author_sort | Alexandra Thiran |
| collection | DOAJ |
| description | Abstract Arthritis is the most common extra‐intestinal complication in inflammatory bowel disease (IBD). Conversely, arthritis patients are at risk for developing IBD and often display subclinical gut inflammation. These observations suggest a shared disease etiology, commonly termed “the gut‐joint‐axis.” The clinical association between gut and joint inflammation is further supported by the success of common therapeutic strategies and microbiota dysbiosis in both conditions. Most data, however, support a correlative relationship between gut and joint inflammation, while causative evidence is lacking. Using two independent transgenic mouse arthritis models, either TNF‐ or IL‐1β dependent, we demonstrate that arthritis develops independently of the microbiota and intestinal inflammation, since both lines develop full‐blown articular inflammation under germ‐free conditions. In contrast, TNF‐driven gut inflammation is fully rescued in germ‐free conditions, indicating that the microbiota is driving TNF‐induced gut inflammation. Together, our study demonstrates that although common inflammatory pathways may drive both gut and joint inflammation, the molecular triggers initiating such pathways are distinct in these tissues. |
| first_indexed | 2024-03-07T16:34:29Z |
| format | Article |
| id | doaj.art-6cc505e181ba4edfa275d745f425476b |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T16:34:29Z |
| publishDate | 2023-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-6cc505e181ba4edfa275d745f425476b2024-03-03T09:51:18ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-10-011510n/an/a10.15252/emmm.202317691Sterile triggers drive joint inflammation in TNF‐ and IL‐1β‐dependent mouse arthritis modelsAlexandra Thiran0Ioanna Petta1Gillian Blancke2Marie Thorp3Guillaume Planckaert4Maude Jans5Vanessa Andries6Korneel Barbry7Elisabeth Gilis8Julie Coudenys9Tino Hochepied10Christian Vanhove11Eric Gracey12Emilie Dumas13Teddy Manuelo14Ivan Josipovic15Geert vanLoo16Dirk Elewaut17Lars Vereecke18Department of Internal Medicine and Pediatrics Ghent University Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumVIB‐UGent Center for Inflammation Research Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumVIB‐UGent Center for Inflammation Research Ghent BelgiumDepartment of Electronics and Information Systems Ghent University, Faculty of Engineering & Architecture Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumDepartment of Physics and Astronomy – Radiation Physics, Faculty of Science, RP‐UGCT Ghent University Ghent BelgiumVIB‐UGent Center for Inflammation Research Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumDepartment of Internal Medicine and Pediatrics Ghent University Ghent BelgiumAbstract Arthritis is the most common extra‐intestinal complication in inflammatory bowel disease (IBD). Conversely, arthritis patients are at risk for developing IBD and often display subclinical gut inflammation. These observations suggest a shared disease etiology, commonly termed “the gut‐joint‐axis.” The clinical association between gut and joint inflammation is further supported by the success of common therapeutic strategies and microbiota dysbiosis in both conditions. Most data, however, support a correlative relationship between gut and joint inflammation, while causative evidence is lacking. Using two independent transgenic mouse arthritis models, either TNF‐ or IL‐1β dependent, we demonstrate that arthritis develops independently of the microbiota and intestinal inflammation, since both lines develop full‐blown articular inflammation under germ‐free conditions. In contrast, TNF‐driven gut inflammation is fully rescued in germ‐free conditions, indicating that the microbiota is driving TNF‐induced gut inflammation. Together, our study demonstrates that although common inflammatory pathways may drive both gut and joint inflammation, the molecular triggers initiating such pathways are distinct in these tissues.https://doi.org/10.15252/emmm.202317691arthritisgerm‐freegut‐joint axisintestinal inflammationmicrobiome |
| spellingShingle | Alexandra Thiran Ioanna Petta Gillian Blancke Marie Thorp Guillaume Planckaert Maude Jans Vanessa Andries Korneel Barbry Elisabeth Gilis Julie Coudenys Tino Hochepied Christian Vanhove Eric Gracey Emilie Dumas Teddy Manuelo Ivan Josipovic Geert vanLoo Dirk Elewaut Lars Vereecke Sterile triggers drive joint inflammation in TNF‐ and IL‐1β‐dependent mouse arthritis models EMBO Molecular Medicine arthritis germ‐free gut‐joint axis intestinal inflammation microbiome |
| title | Sterile triggers drive joint inflammation in TNF‐ and IL‐1β‐dependent mouse arthritis models |
| title_full | Sterile triggers drive joint inflammation in TNF‐ and IL‐1β‐dependent mouse arthritis models |
| title_fullStr | Sterile triggers drive joint inflammation in TNF‐ and IL‐1β‐dependent mouse arthritis models |
| title_full_unstemmed | Sterile triggers drive joint inflammation in TNF‐ and IL‐1β‐dependent mouse arthritis models |
| title_short | Sterile triggers drive joint inflammation in TNF‐ and IL‐1β‐dependent mouse arthritis models |
| title_sort | sterile triggers drive joint inflammation in tnf and il 1β dependent mouse arthritis models |
| topic | arthritis germ‐free gut‐joint axis intestinal inflammation microbiome |
| url | https://doi.org/10.15252/emmm.202317691 |
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