A sphingosine-1-phosphate type 1 receptor agonist inhibits the early T-cell transient following renal ischemia-reperfusion injury.
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.
Lai
L-W
LW
Department of Medicine, University of Arizona, Tucson, Arizona 85724, USA.
Yong
K-C
KC
Igarashi
S
S
Lien
Y-Hh
YH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007668:Kidney / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology; D007682:Kidney Pelvis / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology; D008297:Male; D051379:Mice; D010069:Oxadiazoles / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D013876:Thiophenes / Q000494:pharmacology
D018925:Chemokines; D010069:Oxadiazoles; D049349:Receptors, Lysosphingolipid; C503964:SEW2871; D013876:Thiophenes