A sphingosine-1-phosphate type 1 receptor agonist inhibits the early T-cell transient following renal ischemia-reperfusion injury

L. W. Lai, K. C. Yong, S. Igarashi, Y. H.H. Lien

Research output: Contribution to journalArticle

50 Scopus citations


T cells are thought to be involved in the pathogenesis of renal ischemia-reperfusion injury (IRI); however, earlier studies have not found significant T-cell numbers in the kidney following injury. In this study we test the hypothesis that T cells transiently infiltrate the kidney following reperfusion and leave behind T-cell-derived cytokines such as interferons and interleukins, thus triggering an inflammatory reaction. An early rise of infiltrating T cells was coupled with a decrease in both circulating lymphocytes and CD4+ cells of periarterial lymphocyte aggregates. The renal expression of several chemokines was rapidly and markedly increased by ischemia-reperfusion (IR). Sphingosine-1-phosphate type 1 receptor agonists have been shown to protect kidneys from injury. One of these agonists given before IR significantly reduced histologically assessed renal injury, circulating lymphocyte numbers, and renal T-cell infiltration. This pretreatment did not, however, affect the increase in T-cell chemokines but caused an increase in CD4+ cells in the renal lymphatic system. We conclude that T-cell infiltration is an early event after IRI and is mediated by several chemokines. Sphingosine-1-phosphate receptor agonists reduce renal injury and T-cell infiltration in spite of chemokine generation by inhibiting T-cell mobilization from both renal and extra-renal lymphoid tissue.

Original languageEnglish (US)
Pages (from-to)1223-1231
Number of pages9
JournalKidney International
Issue number12
StatePublished - Jun 1 2007



  • Chemokine
  • EDG1
  • Ischemic renal injury
  • Lymphocyte
  • Renal lymphatics
  • S1P

ASJC Scopus subject areas

  • Nephrology

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