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Sphingosine-1-Phosphate Receptor Type 4 (S1P4) 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 cavity and their subsequent trafficking remain incompletely understood. Sphingosine1-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 S1P1 and S1P4 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 S1P1 and S1P4 are differentially regulated upon stimulation with the TLR4 agonist LPS, but not upon PMA/ionomycin or B cell receptor (BCR) crosslinking. S1P4 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. S1P4 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 S1P4 mediated signaling on the severity and mortality of peritoneal sepsis are warranted.
Author: | Janik Riese, Alina Gromann, Felix Lührs, Annabel Kleinwort, Tobias Schulze |
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URN: | urn:nbn:de:gbv:9-opus-64773 |
DOI: | https://doi.org/10.3390/ijms22073465 |
ISSN: | 1422-0067 |
Parent Title (English): | International Journal of Molecular Sciences |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of first Publication: | 2021/03/27 |
Release Date: | 2022/11/21 |
Tag: | abdominal sepsis; innate response activator B cells (IRA B cells); lymphocyte trafficking; peritoneal B cells; sphingosine-1-phosphate |
GND Keyword: | - |
Volume: | 22 |
Issue: | 7 |
Page Number: | 20 |
Faculties: | Universitätsmedizin / Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie/Plastische Operationen |
Licence (German): | Creative Commons - Namensnennung |