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Volume 21
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10.3390/ijms21176242
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Article

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

by
Alexandra Lucaciu
1,*,
Hannah Kuhn
1,
Sandra Trautmann
2,
Nerea Ferreirós
2,
Helmuth Steinmetz
1,
Josef Pfeilschifter
3,
Robert Brunkhorst
1,4,
Waltraud Pfeilschifter
1,
Julien Subburayalu
5,† and
Rajkumar Vutukuri
3,*,†
1
Department of Neurology, Goethe University Frankfurt, 60528 Frankfurt am Main, Germany
2
Institute of Clinical Pharmacology, Pharmazentrum Frankfurt, Goethe University Frankfurt, 60528 Frankfurt am Main, Germany
3
Institute of General Pharmacology and Toxicology, Pharmazentrum Frankfurt, Goethe University Frankfurt, 60528 Frankfurt am Main, Germany
4
Department of Neurology, RWTH Aachen University, 52074 Aachen, Germany
5
Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally.
Int. J. Mol. Sci. 2020, 21(17), 6242; https://doi.org/10.3390/ijms21176242
Submission received: 7 July 2020 / Revised: 26 August 2020 / Accepted: 26 August 2020 / Published: 28 August 2020
(This article belongs to the Collection Sphingolipid Signaling in Health and Disease)
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Abstract

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 (S1PR). 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 S1PR type 1 (S1P1+) were the predominant population deserting the spleen. Here, we report the cerebral recruitment of T helper (TH) and regulatory T (TREG) cells to the ipsilateral hemisphere, which was associated with differential regulation of cerebral S1PR expression patterns in the brain after MCAO. This study provides insight that the S1P-S1PR axis facilitates splenic T cell egress and is linked to the cerebral recruitment of S1PR+ TH and TREG cells. Further insights by which means the S1P-S1PR-axis orchestrates neuronal positioning may offer new therapeutic perspectives after ischemic stroke.
Keywords: sphingosine 1-phosphate; regulatory T helper cells; stroke; sphingosine kinase; sphingosine 1-phosphate receptor; ceramides; fingolimod sphingosine 1-phosphate; regulatory T helper cells; stroke; sphingosine kinase; sphingosine 1-phosphate receptor; ceramides; fingolimod

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MDPI and ACS Style

Lucaciu, A.; Kuhn, H.; Trautmann, S.; Ferreirós, N.; Steinmetz, H.; Pfeilschifter, J.; Brunkhorst, R.; Pfeilschifter, W.; Subburayalu, J.; Vutukuri, R. A Sphingosine 1-Phosphate Gradient Is Linked to the Cerebral Recruitment of T Helper and Regulatory T Helper Cells during Acute Ischemic Stroke. Int. J. Mol. Sci. 2020, 21, 6242. https://doi.org/10.3390/ijms21176242

AMA Style

Lucaciu A, Kuhn H, Trautmann S, Ferreirós N, Steinmetz H, Pfeilschifter J, Brunkhorst R, Pfeilschifter W, Subburayalu J, Vutukuri R. A Sphingosine 1-Phosphate Gradient Is Linked to the Cerebral Recruitment of T Helper and Regulatory T Helper Cells during Acute Ischemic Stroke. International Journal of Molecular Sciences. 2020; 21(17):6242. https://doi.org/10.3390/ijms21176242

Chicago/Turabian Style

Lucaciu, Alexandra, Hannah Kuhn, Sandra Trautmann, Nerea Ferreirós, Helmuth Steinmetz, Josef Pfeilschifter, Robert Brunkhorst, Waltraud Pfeilschifter, Julien Subburayalu, and Rajkumar Vutukuri. 2020. "A Sphingosine 1-Phosphate Gradient Is Linked to the Cerebral Recruitment of T Helper and Regulatory T Helper Cells during Acute Ischemic Stroke" International Journal of Molecular Sciences 21, no. 17: 6242. https://doi.org/10.3390/ijms21176242

APA Style

Lucaciu, A., Kuhn, H., Trautmann, S., Ferreirós, N., Steinmetz, H., Pfeilschifter, J., Brunkhorst, R., Pfeilschifter, W., Subburayalu, J., & Vutukuri, R. (2020). A Sphingosine 1-Phosphate Gradient Is Linked to the Cerebral Recruitment of T Helper and Regulatory T Helper Cells during Acute Ischemic Stroke. International Journal of Molecular Sciences, 21(17), 6242. https://doi.org/10.3390/ijms21176242

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