A Sphingosine 1-Phosphate Gradient Is Linked to the Cerebral Recruitment of T Helper and Regulatory T Helper Cells during Acute Ischemic Stroke

• Published in: International journal of molecular sciences 2020-08, Vol.21 (17), p.6242
• Main Authors: Lucaciu, Alexandra, Kuhn, Hannah, Trautmann, Sandra, Ferreirós, Nerea, Steinmetz, Helmuth, Pfeilschifter, Josef, Brunkhorst, Robert, Pfeilschifter, Waltraud, Subburayalu, Julien, Vutukuri, Rajkumar
• Format: Article
• Language: English
• Subjects: Animals; Brain - immunology; Brain research; ceramides; Cerebral blood flow; Disease Models, Animal; Egress; Helper cells; Immune system; Ischemia; Ischemic Stroke - etiology; Ischemic Stroke - immunology; Ischemic Stroke - metabolism; Lymphocytes; Lymphocytes T; Lysophospholipids - metabolism; Male; Metabolism; Mice; Mice, Inbred C57BL; Occlusion; Plasma; Recruitment; regulatory T helper cells; Signal Transduction; Sphingosine - analogs & derivatives; Sphingosine - metabolism; Sphingosine 1-phosphate; sphingosine 1-phosphate receptor; sphingosine kinase; Sphingosine-1-Phosphate Receptors - metabolism; Spleen; Spleen - metabolism; Stroke; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Regulatory - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21176242

Emerging evidence suggests a complex relationship between sphingosine 1-phosphate (S1P) signaling and stroke. Here, we show the kinetics of S1P in the acute phase of ischemic stroke and highlight accompanying changes in immune cells and S1P receptors (S1P ). Using a C57BL/6 mouse model of middle cerebral artery occlusion (MCAO), we assessed S1P concentrations in the brain, plasma, and spleen. We found a steep S1P gradient from the spleen towards the brain. Results obtained by qPCR suggested that cells expressing the S1P type 1 (S1P ) were the predominant population deserting the spleen. Here, we report the cerebral recruitment of T helper (T ) and regulatory T (T ) cells to the ipsilateral hemisphere, which was associated with differential regulation of cerebral S1P expression patterns in the brain after MCAO. This study provides insight that the S1P-S1P axis facilitates splenic T cell egress and is linked to the cerebral recruitment of S1P T and T cells. Further insights by which means the S1P-S1P -axis orchestrates neuronal positioning may offer new therapeutic perspectives after ischemic stroke.