Sphingosine-1-phosphate promotes the persistence of activated CD4 T cells in inflamed sites

Jaigrdar, S. A., Benson, R. A. , Elmesmari, A., Kurowska-Stolarska, M. S. , McInnes, I. B. , Garside, P. and Macleod, M. K.L. (2017) Sphingosine-1-phosphate promotes the persistence of activated CD4 T cells in inflamed sites. Frontiers in Immunology, 8, 1627. (doi: 10.3389/fimmu.2017.01627) (PMID:29225602) (PMCID:PMC5705559)

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Inflammation can be protective or pathogenic depending on context and timeframe. Acute inflammation, including the accumulation of CD4 T cells, accompanies protective immune responses to pathogens, but the presence of activated CD4 T cells at sites of inflammation is associated with chronic inflammatory disease. While significant progress has been made in understanding the migration of CD4 T cells into inflamed sites, the signals that lead to their persistence are poorly characterized. Using a murine ear model of acute inflammation and intravital two-photon imaging, we have dissected the signals that mediate CD4 T cell persistence. We report the unexpected finding that the bioactive lipid, sphingosine-1-phosphate (S1P), is both necessary and sufficient for the persistence of activated CD4 T cells at peripheral tissues in acute inflammation. S1P mediated the enhanced motility of CD4 T cells at inflamed tissues but did not affect their migration to the downstream draining lymph node. We found that sphingosine kinase-1, which regulates S1P production is increased at inflamed sites in mice and in patients with the chronic inflammatory disease, rheumatoid arthritis. Together, these data suggest that S1P, or its regulators, may be key targets to promote or disrupt accumulation of CD4 T cells at inflamed tissues.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Elmesmari, Dr Aziza and Garside, Professor Paul and Macleod, Dr Megan and Benson, Dr Robert and Kurowska-Stolarska, Professor Mariola
Authors: Jaigrdar, S. A., Benson, R. A., Elmesmari, A., Kurowska-Stolarska, M. S., McInnes, I. B., Garside, P., and Macleod, M. K.L.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Frontiers in Immunology
ISSN (Online):1664-3224
Published Online:24 November 2017
Copyright Holders:Copyright © 2017 Jaigirdar, Benson, Elmesmari, Kurowska-Stolarska, McInnes, Garside and MacLeod.
First Published:First published in Frontiers in Immunology 8:1627
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
581051Molecular requirements for the induction of tolerance in activated and memory CD4 T cells.Megan MacLeodArthritis Research UK (ARTRESUK)19905III -IMMUNOLOGY
632301Control of T Cell retention at inflammatory sitesMegan MacLeodArthritis Research UK (ARTRESUK)20339III -IMMUNOLOGY