The emerging alliance of sphingosine-1-phosphate signalling and immune cells: from basic mechanisms to implications in hypertension.

The immune system plays a considerable role in hypertension. In particular, T-lymphocytes are recognized as important players in its pathogenesis. Despite substantial experimental efforts, the molecular mechanisms underlying the nature of T-cell activation contributing to an onset of hypertension or disease perpetuation are still elusive. Amongst other cell types, lymphocytes express distinct profiles of GPCRs for sphingosine-1-phosphate (S1P) - a bioactive phospholipid that is involved in many critical cell processes and most importantly majorly regulates T-cell development, lymphocyte recirculation, tissue-homing patterns and chemotactic responses. Recent findings have revealed a key role for S1P chemotaxis and T-cell mobilization for the onset of experimental hypertension, and elevated circulating S1P levels have been linked to several inflammation-associated diseases including hypertension in patients. In this article, we review the recent progress towards understanding how S1P and its receptors regulate immune cell trafficking and function and its potential relevance for the pathophysiology of hypertension. LINKED ARTICLES: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc.