{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T23:58:58Z","timestamp":1776988738127,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T00:00:00Z","timestamp":1616803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2011quantitatively 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)\u2011induced 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.<\/jats:p>","DOI":"10.3390\/ijms22073465","type":"journal-article","created":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T22:09:01Z","timestamp":1616969341000},"page":"3465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["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"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0701-060X","authenticated-orcid":false,"given":"Janik","family":"Riese","sequence":"first","affiliation":[{"name":"Experimental Surgical Research Laboratory, Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universit\u00e4tsmedizin Greifswald, 17475 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Gromann","sequence":"additional","affiliation":[{"name":"Experimental Surgical Research Laboratory, Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universit\u00e4tsmedizin Greifswald, 17475 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9859-1245","authenticated-orcid":false,"given":"Felix","family":"L\u00fchrs","sequence":"additional","affiliation":[{"name":"Experimental Surgical Research Laboratory, Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universit\u00e4tsmedizin Greifswald, 17475 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annabel","family":"Kleinwort","sequence":"additional","affiliation":[{"name":"Experimental Surgical Research Laboratory, Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universit\u00e4tsmedizin Greifswald, 17475 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Schulze","sequence":"additional","affiliation":[{"name":"Experimental Surgical Research Laboratory, Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universit\u00e4tsmedizin Greifswald, 17475 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1001\/jama.2020.2717","article-title":"Prevalence and Outcomes of Infection Among Patients in Intensive Care Units in 2017","volume":"323","author":"Vincent","year":"2020","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1007\/s00134-019-05819-3","article-title":"Epidemiology of intra-abdominal infection and sepsis in critically ill patients: \"AbSeS\", a multinational observational cohort study and ESICM Trials Group Project","volume":"45","author":"Blot","year":"2019","journal-title":"Intensive Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.1159\/000334169","article-title":"Regulation of experimental peritonitis: A complex orchestration","volume":"120","author":"Laurin","year":"2012","journal-title":"Nephron. 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