The endogenous molecules high-mobility group box 1 (HMGB1) and interleukin-33 (IL-33) have been recognized as alarmins, capable of mediating danger signals during tissue damage. Here, we address their possible role as innate-immune mediators in ischemia-reperfusion injury (IRI) following human kidney transplantation. Urinary HMGB1 and IL-33 levels were significantly increased as soon as 30 min after reperfusion, as compared to prior transplantation. Moreover, a significant correlation was shown between both serum and urinary IL-33 (but not HMGB1) levels and cold ischemia time, from 30 min to 3 days post-tranplantation. In vitro, human umbilical vein endothelial cells submitted to hypoxia-reoxygenation significantly released IL-33. Finally, we can propose that PBMC from renal recipient patients are targeted by both HMGB1 and IL-33 as their receptor (TLR2/4 and ST2-L, respectively) transcripts were enhanced early after transplantation. Consistent with this view, by analyzing iNKT cells, which are been suggested to play a crucial role in IRI and we recently reported to be targeted by IL-33, we showed an early activation state of this innate-like T cell subset in kidney transplant recipients, as attested by the upregulation of CD69 surface expression 1 hour after transplantation. Altogether, these results underline the possible role of IL-33 as an innate-immune mediator during IRI in humans.
- Copyright © 2013 by The American Association of Immunologists, Inc.