CXCR1 drives the pathogenesis of EAE and ARDS via boosting dendritic cells-dependent inflammation
Abstract Chemokines secreted by dendritic cells (DCs) play a key role in the regulation of inflammation and autoimmunity through chemokine receptors. However, the role of chemokine receptor CXCR1 in inflammation-inducing experimental autoimmune encephalomyelitis (EAE) and acute respiratory distress...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-09-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06126-y |
| _version_ | 1797682610342723584 |
|---|---|
| author | Wei Zhuang Jinfeng Zhou Lan Zhong Jie Lv Xuan Zhong Guangyu Liu Ling Xie Chun Wang Kaidireya Saimaier Sanxing Han Changjie Shi Qiuhong Hua Ru Zhang Xin Xie Changsheng Du |
| author_facet | Wei Zhuang Jinfeng Zhou Lan Zhong Jie Lv Xuan Zhong Guangyu Liu Ling Xie Chun Wang Kaidireya Saimaier Sanxing Han Changjie Shi Qiuhong Hua Ru Zhang Xin Xie Changsheng Du |
| author_sort | Wei Zhuang |
| collection | DOAJ |
| description | Abstract Chemokines secreted by dendritic cells (DCs) play a key role in the regulation of inflammation and autoimmunity through chemokine receptors. However, the role of chemokine receptor CXCR1 in inflammation-inducing experimental autoimmune encephalomyelitis (EAE) and acute respiratory distress syndrome (ARDS) remains largely enigmatic. Here we reported that compared with healthy controls, the level of CXCR1 was aberrantly increased in multiple sclerosis (MS) patients. Knockout of CXCR1 not only ameliorated disease severity in EAE mice but also suppressed the secretion of inflammatory factors (IL-6/IL-12p70) production. We observed the same results in EAE mice with DCs-specific deletion of CXCR1 and antibody neutralization of the ligand CXCL5. Mechanically, we demonstrated a positive feedback loop composed of CXCL5/CXCR1/HIF-1α direct regulating of IL-6/IL-12p70 production in DCs. Meanwhile, we found CXCR1 deficiency in DCs limited IL-6/IL-12p70 production and lung injury in LPS-induced ARDS, a disease model caused by inflammation. Overall, our study reveals CXCR1 governs DCs-mediated inflammation and autoimmune disorders and its potential as a therapeutic target for related diseases. |
| first_indexed | 2024-03-12T00:02:19Z |
| format | Article |
| id | doaj.art-91b0031acacd42db85816d091deacc32 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-12T00:02:19Z |
| publishDate | 2023-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-91b0031acacd42db85816d091deacc322023-09-17T11:29:24ZengNature Publishing GroupCell Death and Disease2041-48892023-09-0114911410.1038/s41419-023-06126-yCXCR1 drives the pathogenesis of EAE and ARDS via boosting dendritic cells-dependent inflammationWei Zhuang0Jinfeng Zhou1Lan Zhong2Jie Lv3Xuan Zhong4Guangyu Liu5Ling Xie6Chun Wang7Kaidireya Saimaier8Sanxing Han9Changjie Shi10Qiuhong Hua11Ru Zhang12Xin Xie13Changsheng Du14Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityDepartment of Gastroenterology, Shanghai East Hospital, Tongji University School of MedicineKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityDepartment of Gastroenterology, Shanghai East Hospital, Tongji University School of MedicineKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityAbstract Chemokines secreted by dendritic cells (DCs) play a key role in the regulation of inflammation and autoimmunity through chemokine receptors. However, the role of chemokine receptor CXCR1 in inflammation-inducing experimental autoimmune encephalomyelitis (EAE) and acute respiratory distress syndrome (ARDS) remains largely enigmatic. Here we reported that compared with healthy controls, the level of CXCR1 was aberrantly increased in multiple sclerosis (MS) patients. Knockout of CXCR1 not only ameliorated disease severity in EAE mice but also suppressed the secretion of inflammatory factors (IL-6/IL-12p70) production. We observed the same results in EAE mice with DCs-specific deletion of CXCR1 and antibody neutralization of the ligand CXCL5. Mechanically, we demonstrated a positive feedback loop composed of CXCL5/CXCR1/HIF-1α direct regulating of IL-6/IL-12p70 production in DCs. Meanwhile, we found CXCR1 deficiency in DCs limited IL-6/IL-12p70 production and lung injury in LPS-induced ARDS, a disease model caused by inflammation. Overall, our study reveals CXCR1 governs DCs-mediated inflammation and autoimmune disorders and its potential as a therapeutic target for related diseases.https://doi.org/10.1038/s41419-023-06126-y |
| spellingShingle | Wei Zhuang Jinfeng Zhou Lan Zhong Jie Lv Xuan Zhong Guangyu Liu Ling Xie Chun Wang Kaidireya Saimaier Sanxing Han Changjie Shi Qiuhong Hua Ru Zhang Xin Xie Changsheng Du CXCR1 drives the pathogenesis of EAE and ARDS via boosting dendritic cells-dependent inflammation Cell Death and Disease |
| title | CXCR1 drives the pathogenesis of EAE and ARDS via boosting dendritic cells-dependent inflammation |
| title_full | CXCR1 drives the pathogenesis of EAE and ARDS via boosting dendritic cells-dependent inflammation |
| title_fullStr | CXCR1 drives the pathogenesis of EAE and ARDS via boosting dendritic cells-dependent inflammation |
| title_full_unstemmed | CXCR1 drives the pathogenesis of EAE and ARDS via boosting dendritic cells-dependent inflammation |
| title_short | CXCR1 drives the pathogenesis of EAE and ARDS via boosting dendritic cells-dependent inflammation |
| title_sort | cxcr1 drives the pathogenesis of eae and ards via boosting dendritic cells dependent inflammation |
| url | https://doi.org/10.1038/s41419-023-06126-y |
| work_keys_str_mv | AT weizhuang cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT jinfengzhou cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT lanzhong cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT jielv cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT xuanzhong cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT guangyuliu cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT lingxie cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT chunwang cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT kaidireyasaimaier cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT sanxinghan cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT changjieshi cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT qiuhonghua cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT ruzhang cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT xinxie cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation AT changshengdu cxcr1drivesthepathogenesisofeaeandardsviaboostingdendriticcellsdependentinflammation |