Beyond Immune Cell Migration: The Emerging Role of the Sphingosine-1-phosphate Receptor S1PR4 as a Modulator of Innate Immune Cell Activation

Mediators Inflamm. 2017;2017:6059203. doi: 10.1155/2017/6059203. Epub 2017 Aug 7.


The sphingolipid sphingosine-1-phosphate (S1P) emerges as an important regulator of immunity, mainly by signaling through a family of five specific G protein-coupled receptors (S1PR1-5). While S1P signaling generally has the potential to affect not only trafficking but also differentiation, activation, and survival of a diverse range of immune cells, the specific outcome depends on the S1P receptor repertoire expressed on a given cell. Among the S1PRs, S1PR4 is specifically abundant in immune cells, suggesting a major role of the S1P/S1PR4 axis in immunity. Recent studies indeed highlight its role in activation of immune cells, differentiation, and, potentially, trafficking. In this review, we summarize the emerging data that support a major role of S1PR4 in modulating immunity in humans and mice and discuss therapeutic implications.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Humans
  • Lysophospholipids / metabolism*
  • Signal Transduction / physiology
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism


  • Lysophospholipids
  • sphingosine 1-phosphate
  • Sphingosine