Exit Strategies: S1P Signaling and T Cell Migration. Issue 12 (December 2015)

• Record Type: Journal Article
• Authors: Baeyens, Audrey; Fang, Victoria; Chen, Cynthia; Schwab, Susan R.
• Is Part Of: Trends in immunology. Volume 36:Issue 12(2015)
• Page Start: 778
• Page End: 787
• Publication Date: 2015-12
• Subjects: Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2015.10.005
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : Whereas the role of sphingosine 1-phosphate receptor 1 (S1PR1) in T cell egress and the regulation of S1P gradients between lymphoid organs and circulatory fluids in homeostasis are increasingly well understood, much remains to be learned about S1P signaling and distribution during an immune response. Recent data suggest that the role of S1PR1 in directing cells from tissues into circulatory fluids is reprised again and again, particularly in guiding activated T cells from non-lymphoid tissues into lymphatics. Conversely, S1P receptor 2 (S1PR2), which antagonizes migration towards chemokines, confines cells within tissues. Here we review the current understanding of the roles of S1P signaling in activated T cell migration. In this context, we outline open questions, particularly regarding the shape of S1P gradients in different tissues in homeostasis and inflammation, and discuss recent strategies to measure S1P. Trends: S1PR1 signaling guides T cells out of lymph nodes, and T cells balance the pull of S1P with retention cues from chemokines within the lymph nodes. The relative weight of these signals changes over the course of an immune response. S1PR2 signaling, by contrast, retains follicular T helper (Tfh) cells in germinal centers (GCs). S1PR2 is expressed in high amounts in Tfh cells that localize to GCs, and genetic deletion of S1pr2 leads to lower numbers of Tfh cells in GC. S1PR1 signaling regulates effector T cell residence time in non-lymphoid tissues, with many parallels to S1PR1 function in lymphoid organs. S1PR1 is downregulated in CD8 + resident memory T (TRM) cells in many tissues, and forced expression leads to failed establishment of TRM cells. Cytokines in the tissue environment induce downregulation of KLF2, a transcription factor that induces expression of S1PR1.