Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4
Emerging evidence suggests a mechanistic role for myeloid-derived suppressor cells (MDSCs) in lung diseases like asthma. Previously, we showed that adoptive transfer of MDSCs dampens lung inflammation in murine models of asthma through cyclooxygenase-2 and arginase-1 pathways. Here, we further disse...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.695933/full |
| _version_ | 1818883837422206976 |
|---|---|
| author | Chiel van Geffen Chiel van Geffen Chiel van Geffen Astrid Deißler Sandra Beer-Hammer Bernd Nürnberg Rupert Handgretinger Harald Renz Harald Renz Dominik Hartl Dominik Hartl Saeed Kolahian Saeed Kolahian Saeed Kolahian |
| author_facet | Chiel van Geffen Chiel van Geffen Chiel van Geffen Astrid Deißler Sandra Beer-Hammer Bernd Nürnberg Rupert Handgretinger Harald Renz Harald Renz Dominik Hartl Dominik Hartl Saeed Kolahian Saeed Kolahian Saeed Kolahian |
| author_sort | Chiel van Geffen |
| collection | DOAJ |
| description | Emerging evidence suggests a mechanistic role for myeloid-derived suppressor cells (MDSCs) in lung diseases like asthma. Previously, we showed that adoptive transfer of MDSCs dampens lung inflammation in murine models of asthma through cyclooxygenase-2 and arginase-1 pathways. Here, we further dissected this mechanism by studying the role and therapeutic relevance of the downstream mediator prostaglandin E2 receptor 4 (EP4) in a murine model of asthma. We adoptively transferred MDSCs generated using an EP4 agonist in a murine model of asthma and studied the consequences on airway inflammation. Furthermore, pegylated human arginase-1 was used to model MDSC effector activities. We demonstrate that the selective EP4 agonist L-902,688 increased the number and suppressive activity of MDSCs through arginase-1 and nitric oxide synthase-2. These results showed that adoptive transfer of EP4-primed MDSCs, EP4 agonism alone or arginase-1 administration ameliorated lung inflammatory responses and histopathological changes in asthmatic mice. Collectively, our results provide evidence that MDSCs dampen airway inflammation in murine asthma through a mechanism involving EP4. |
| first_indexed | 2024-12-19T15:40:00Z |
| format | Article |
| id | doaj.art-04980a933f934f31b517642ef2f5c94b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T15:40:00Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-04980a933f934f31b517642ef2f5c94b2022-12-21T20:15:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.695933695933Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4Chiel van Geffen0Chiel van Geffen1Chiel van Geffen2Astrid Deißler3Sandra Beer-Hammer4Bernd Nürnberg5Rupert Handgretinger6Harald Renz7Harald Renz8Dominik Hartl9Dominik Hartl10Saeed Kolahian11Saeed Kolahian12Saeed Kolahian13Department of Experimental and Clinical Pharmacology and Pharmacogenomics, University Hospital Tübingen, Tübingen, GermanyInstitute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University of Marburg, Marburg, GermanyUniversities of Giessen and Marburg Lung Center, German Center for Lung Research (DZL), Marburg, GermanyDepartment of Experimental and Clinical Pharmacology and Pharmacogenomics, University Hospital Tübingen, Tübingen, GermanyDepartment of Pharmacology, Experimental Therapy & Toxicology and Interfaculty Center of Pharmacogenomics & Drug Research (IZePhA), University Hospitals and Clinics, Eberhard Karls University Tübingen, Tübingen, GermanyDepartment of Pharmacology, Experimental Therapy & Toxicology and Interfaculty Center of Pharmacogenomics & Drug Research (IZePhA), University Hospitals and Clinics, Eberhard Karls University Tübingen, Tübingen, GermanyChildren’s University Hospital, Eberhard Karls University of Tübingen, Tübingen, GermanyInstitute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University of Marburg, Marburg, GermanyUniversities of Giessen and Marburg Lung Center, German Center for Lung Research (DZL), Marburg, GermanyDepartment of Pediatrics I, Eberhard Karls University of Tübingen, Tübingen, GermanyTranslational Medicine, Novartis Institutes for BioMedical Research, Basel, SwitzerlandDepartment of Experimental and Clinical Pharmacology and Pharmacogenomics, University Hospital Tübingen, Tübingen, GermanyInstitute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University of Marburg, Marburg, GermanyUniversities of Giessen and Marburg Lung Center, German Center for Lung Research (DZL), Marburg, GermanyEmerging evidence suggests a mechanistic role for myeloid-derived suppressor cells (MDSCs) in lung diseases like asthma. Previously, we showed that adoptive transfer of MDSCs dampens lung inflammation in murine models of asthma through cyclooxygenase-2 and arginase-1 pathways. Here, we further dissected this mechanism by studying the role and therapeutic relevance of the downstream mediator prostaglandin E2 receptor 4 (EP4) in a murine model of asthma. We adoptively transferred MDSCs generated using an EP4 agonist in a murine model of asthma and studied the consequences on airway inflammation. Furthermore, pegylated human arginase-1 was used to model MDSC effector activities. We demonstrate that the selective EP4 agonist L-902,688 increased the number and suppressive activity of MDSCs through arginase-1 and nitric oxide synthase-2. These results showed that adoptive transfer of EP4-primed MDSCs, EP4 agonism alone or arginase-1 administration ameliorated lung inflammatory responses and histopathological changes in asthmatic mice. Collectively, our results provide evidence that MDSCs dampen airway inflammation in murine asthma through a mechanism involving EP4.https://www.frontiersin.org/articles/10.3389/fimmu.2021.695933/fullmyeloid-derived suppressor cellsprostaglandin E2E-prostanoid receptorsarginase-1airway inflammationasthma |
| spellingShingle | Chiel van Geffen Chiel van Geffen Chiel van Geffen Astrid Deißler Sandra Beer-Hammer Bernd Nürnberg Rupert Handgretinger Harald Renz Harald Renz Dominik Hartl Dominik Hartl Saeed Kolahian Saeed Kolahian Saeed Kolahian Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4 Frontiers in Immunology myeloid-derived suppressor cells prostaglandin E2 E-prostanoid receptors arginase-1 airway inflammation asthma |
| title | Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4 |
| title_full | Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4 |
| title_fullStr | Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4 |
| title_full_unstemmed | Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4 |
| title_short | Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4 |
| title_sort | myeloid derived suppressor cells dampen airway inflammation through prostaglandin e2 receptor 4 |
| topic | myeloid-derived suppressor cells prostaglandin E2 E-prostanoid receptors arginase-1 airway inflammation asthma |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.695933/full |
| work_keys_str_mv | AT chielvangeffen myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT chielvangeffen myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT chielvangeffen myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT astriddeißler myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT sandrabeerhammer myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT berndnurnberg myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT ruperthandgretinger myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT haraldrenz myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT haraldrenz myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT dominikhartl myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT dominikhartl myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT saeedkolahian myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT saeedkolahian myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 AT saeedkolahian myeloidderivedsuppressorcellsdampenairwayinflammationthroughprostaglandine2receptor4 |