Sphingosine-1-Phosphate Receptor Type 4 (S1P<sub>4</sub>) Is Differentially Regulated in Peritoneal B1 B Cells upon TLR4 Stimulation and Facilitates the Egress of Peritoneal B1a B Cells and Subsequent Accumulation of Splenic IRA B Cells under Inflammatory Conditions
Background: Gram-negative infections of the peritoneal cavity result in profound modifications of peritoneal B cell populations and induce the migration of peritoneal B cells to distant secondary lymphoid organs. However, mechanisms controlling the egress of peritoneal B cells from the peritoneal ca...
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3465 |
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| author | Janik Riese Alina Gromann Felix Lührs Annabel Kleinwort Tobias Schulze |
| author_facet | Janik Riese Alina Gromann Felix Lührs Annabel Kleinwort Tobias Schulze |
| author_sort | Janik Riese |
| collection | DOAJ |
| description | Background: Gram-negative infections of the peritoneal cavity result in profound modifications of peritoneal B cell populations and induce the migration of peritoneal B cells to distant secondary lymphoid organs. However, mechanisms controlling the egress of peritoneal B cells from the peritoneal cavity and their subsequent trafficking remain incompletely understood. Sphingosine-1-phosphate (S1P)-mediated signaling controls migratory processes in numerous immune cells. The present work investigates the role of S1P-mediated signaling in peritoneal B cell trafficking under inflammatory conditions. Methods: Differential S1P receptor expression after peritoneal B cell activation was assessed semi‑quantitatively using RT-PCR in vitro. The functional implications of differential S1P<sub>1</sub> and S1P<sub>4</sub> expression were assessed by transwell migration in vitro, by adoptive peritoneal B cell transfer in a model of sterile lipopolysaccharide (LPS)‑induced peritonitis and in the polymicrobial colon ascendens stent peritonitis (CASP) model. Results: The two sphingosine-1-phosphate receptors (S1PRs) expressed in peritoneal B cell subsets S1P<sub>1</sub> and S1P<sub>4</sub> are differentially regulated upon stimulation with the TLR4 agonist LPS, but not upon PMA/ionomycin or B cell receptor (BCR) crosslinking. S1P<sub>4</sub> deficiency affects both the trafficking of activated peritoneal B cells to secondary lymphoid organs and the positioning of these cells within the functional compartments of the targeted organ. S1P<sub>4</sub> deficiency in LPS-activated peritoneal B cells results in significantly reduced numbers of splenic innate response activator B cells. Conclusions: The S1P-S1PR system is implicated in the trafficking of LPS-activated peritoneal B cells. Given the protective role of peritoneal B1a B cells in peritoneal sepsis, further experiments to investigate the impact of S1P<sub>4</sub>-mediated signaling on the severity and mortality of peritoneal sepsis are warranted. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:51:29Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a0c8dcef4ac8412daee11f8de9a851a42023-11-21T13:04:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01227346510.3390/ijms22073465Sphingosine-1-Phosphate Receptor Type 4 (S1P<sub>4</sub>) Is Differentially Regulated in Peritoneal B1 B Cells upon TLR4 Stimulation and Facilitates the Egress of Peritoneal B1a B Cells and Subsequent Accumulation of Splenic IRA B Cells under Inflammatory ConditionsJanik Riese0Alina Gromann1Felix Lührs2Annabel Kleinwort3Tobias Schulze4Experimental Surgical Research Laboratory, Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universitätsmedizin Greifswald, 17475 Greifswald, GermanyExperimental Surgical Research Laboratory, Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universitätsmedizin Greifswald, 17475 Greifswald, GermanyExperimental Surgical Research Laboratory, Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universitätsmedizin Greifswald, 17475 Greifswald, GermanyExperimental Surgical Research Laboratory, Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universitätsmedizin Greifswald, 17475 Greifswald, GermanyExperimental Surgical Research Laboratory, Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universitätsmedizin Greifswald, 17475 Greifswald, GermanyBackground: Gram-negative infections of the peritoneal cavity result in profound modifications of peritoneal B cell populations and induce the migration of peritoneal B cells to distant secondary lymphoid organs. However, mechanisms controlling the egress of peritoneal B cells from the peritoneal cavity and their subsequent trafficking remain incompletely understood. Sphingosine-1-phosphate (S1P)-mediated signaling controls migratory processes in numerous immune cells. The present work investigates the role of S1P-mediated signaling in peritoneal B cell trafficking under inflammatory conditions. Methods: Differential S1P receptor expression after peritoneal B cell activation was assessed semi‑quantitatively using RT-PCR in vitro. The functional implications of differential S1P<sub>1</sub> and S1P<sub>4</sub> expression were assessed by transwell migration in vitro, by adoptive peritoneal B cell transfer in a model of sterile lipopolysaccharide (LPS)‑induced peritonitis and in the polymicrobial colon ascendens stent peritonitis (CASP) model. Results: The two sphingosine-1-phosphate receptors (S1PRs) expressed in peritoneal B cell subsets S1P<sub>1</sub> and S1P<sub>4</sub> are differentially regulated upon stimulation with the TLR4 agonist LPS, but not upon PMA/ionomycin or B cell receptor (BCR) crosslinking. S1P<sub>4</sub> deficiency affects both the trafficking of activated peritoneal B cells to secondary lymphoid organs and the positioning of these cells within the functional compartments of the targeted organ. S1P<sub>4</sub> deficiency in LPS-activated peritoneal B cells results in significantly reduced numbers of splenic innate response activator B cells. Conclusions: The S1P-S1PR system is implicated in the trafficking of LPS-activated peritoneal B cells. Given the protective role of peritoneal B1a B cells in peritoneal sepsis, further experiments to investigate the impact of S1P<sub>4</sub>-mediated signaling on the severity and mortality of peritoneal sepsis are warranted.https://www.mdpi.com/1422-0067/22/7/3465sphingosine-1-phosphateperitoneal B cellsabdominal sepsislymphocyte traffickinginnate response activator B cells (IRA B cells) |
| spellingShingle | Janik Riese Alina Gromann Felix Lührs Annabel Kleinwort Tobias Schulze Sphingosine-1-Phosphate Receptor Type 4 (S1P<sub>4</sub>) Is Differentially Regulated in Peritoneal B1 B Cells upon TLR4 Stimulation and Facilitates the Egress of Peritoneal B1a B Cells and Subsequent Accumulation of Splenic IRA B Cells under Inflammatory Conditions International Journal of Molecular Sciences sphingosine-1-phosphate peritoneal B cells abdominal sepsis lymphocyte trafficking innate response activator B cells (IRA B cells) |
| title | Sphingosine-1-Phosphate Receptor Type 4 (S1P<sub>4</sub>) Is Differentially Regulated in Peritoneal B1 B Cells upon TLR4 Stimulation and Facilitates the Egress of Peritoneal B1a B Cells and Subsequent Accumulation of Splenic IRA B Cells under Inflammatory Conditions |
| title_full | Sphingosine-1-Phosphate Receptor Type 4 (S1P<sub>4</sub>) Is Differentially Regulated in Peritoneal B1 B Cells upon TLR4 Stimulation and Facilitates the Egress of Peritoneal B1a B Cells and Subsequent Accumulation of Splenic IRA B Cells under Inflammatory Conditions |
| title_fullStr | Sphingosine-1-Phosphate Receptor Type 4 (S1P<sub>4</sub>) Is Differentially Regulated in Peritoneal B1 B Cells upon TLR4 Stimulation and Facilitates the Egress of Peritoneal B1a B Cells and Subsequent Accumulation of Splenic IRA B Cells under Inflammatory Conditions |
| title_full_unstemmed | Sphingosine-1-Phosphate Receptor Type 4 (S1P<sub>4</sub>) Is Differentially Regulated in Peritoneal B1 B Cells upon TLR4 Stimulation and Facilitates the Egress of Peritoneal B1a B Cells and Subsequent Accumulation of Splenic IRA B Cells under Inflammatory Conditions |
| title_short | Sphingosine-1-Phosphate Receptor Type 4 (S1P<sub>4</sub>) Is Differentially Regulated in Peritoneal B1 B Cells upon TLR4 Stimulation and Facilitates the Egress of Peritoneal B1a B Cells and Subsequent Accumulation of Splenic IRA B Cells under Inflammatory Conditions |
| title_sort | sphingosine 1 phosphate receptor type 4 s1p sub 4 sub is differentially regulated in peritoneal b1 b cells upon tlr4 stimulation and facilitates the egress of peritoneal b1a b cells and subsequent accumulation of splenic ira b cells under inflammatory conditions |
| topic | sphingosine-1-phosphate peritoneal B cells abdominal sepsis lymphocyte trafficking innate response activator B cells (IRA B cells) |
| url | https://www.mdpi.com/1422-0067/22/7/3465 |
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