Mediators of Inflammation / 2016 / Article / Fig 2

Review Article

Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential

Figure 2

S1P-S1PR1 axis and lymphocyte retention in inflamed tissue. Surface expression of S1PR1 and S1PR4 on T cells is induced by chemokines CXCL9−CXCL11 presented on the endothelial surface and results in T cell migration into inflamed tissue. This is mediated at least partially by interactions of adhesion molecules LFA-1/ICAM-1 and VLA-4/VCAM-1. GRK2 downregulates S1PR1, allowing them to be retained in inflamed tissues. Downregulation of transcription factor KLF2 and S1PR1 transcription provides T cell retention in tissue, which is associated by early CD69 expression. CXCL: C-X-C chemokine ligand; CXCR3; C-X-C chemokine receptor 3; LFA-1: lymphocyte function-associated antigen-1; ICAM-1: intercellular adhesion molecule-1; VLA-4: very late antigen-4; VCAM-1: vascular cell adhesion molecule-1; GRK2: guanine nucleotide-binding protein-coupled receptor kinase-2; KLF2: Krüppel-like factor 2.