Login to Access Video or Poster Abstract: MP74-19
Sources of Funding: none

Introduction

Solid organ transplantation inevitably leads to ischemia-reperfusion injury (IRI).?Regulatory T cells (Tregs) are involved in immunological tolerance at the transplantation site, especially with respect to natural immunity, and also have anti-inflammatory effects. The present study aimed to evaluate whether Tregs protect the kidney from IRI and to explore the possible underlying mechanism.

Methods

We established the IRI model in male mice (C57BL/6, 10–12 weeks old). Left renal ischemia was performed for 30 min, and then the right kidney was resected following left renal reperfusion. We administered tricostatin A (TsA) and PC61 (anti-CD25 mAb) to increase and decrease the number of Tregs, respectively. Mice were divided into the four groups: the TsA group, the DMSO (vehicle) group, the TsA + PC61 group, and the DMSO + PC61 group. Splenic Treg fractions (CD4[+]Foxp3[+]) were evaluated by flow cytometry at postoperative day (POD) 7. Serum levels of creatinine and different inflammatory cytokines, such as IL-10, IL-6, IL-2, and TNF, were measured by ELISA. The mRNA expressions of Foxp3, IL-10, IL-6, TGF-B, CD80, CD86, and ICAM-1 in the kidney at POD2 were measured by real-time qRT-PCR.

Results

The splenic Treg fraction in the TsA group was significantly higher than those in the other three groups (p < 0.001, respectively). At POD2, the mean level of serum creatinine in the TsA group was significantly lower than those in the other three groups (p < 0.001, respectively). The mean level of serum IL-10 in the TsA group was significantly higher than those in the DMSO/DMSO + PC61 groups (p = 0.01), whereas the mean level of serum IL-6 in the TsA group was significantly lower than those in the DMSO/DMSO + PC61 groups (p = 0.003, respectively). The renal expressions of Foxp3 and IL-10 mRNA were significantly higher in the TsA group than those in the DMSO group (p = 0.003 and p = 0.03, respectively). In contrast to the above findings, the IL-6 mRNA expression was significantly lower in the TsA group than that in the DMSO group (p = 0.016). The mRNA expressions of CD80, CD86, and ICAM-1 in the kidney were significantly lower in the TsA group than those in the DMSO group (p < 0.001, p = 0.018, p = 0.004, respectively).

Conclusions

Facilitation of Treg expansion by TsA might have some roles in the protection of the kidney from IRI by reducing the expression of co-stimulatory molecules.

Funding

none