Original Research ARTICLE
Sphingosine-1-phosphate promotes the persistence of activated CD4 T cells in inflamed sites
- 1University of Glasgow, United Kingdom
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.
Keywords: Inflammation, CD4 T cell, Sphingosine-1-phosphate, Migration, intravital imaging, Rheumatoid arthritis
Received: 15 Aug 2017;
Accepted: 09 Nov 2017.
Edited by:Kim Midwood, University of Oxford, United Kingdom
Reviewed by:Gareth W. Jones, Cardiff University, United Kingdom
Clare L. Bennett, University College London, United Kingdom
Copyright: © 2017 Jaigrdar, Benson, Elmesmari, Kurowska-Stolarska, McInnes, Garside and Macleod. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Megan K. Macleod, University of Glasgow, Glasgow, United Kingdom, firstname.lastname@example.org