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Background. Seventy-two hours of preoperative fasting (FA) or 2 weeks of 30% dietary restriction (DR) offers robust protection against renal ischemia-reperfusion injury (IRI) in mice. However, the mechanism remains to be elucidated. We hypothesize that immunomodulation plays a pivotal role. We have shown that the adaptive immune system undergoes major changes due to dietary interventions. Adaptive immunity plays an important role during the course of IRI. Therefore, we investigated the impact of fasting and dietary restriction on unconventional T cells, recently described in relation to IRI. Materials and Methods. Male C57Bl/6 mice were fed ad libitum (AL) or underwent 72 hours fasting (FA) or 30% dietary restriction for 2 weeks (n=8/group). Kidneys were harvested after dietary interventions (t=0hrs) for histological study, immunohistochemistry and rtPCR. In another group, mice were subjected to the three dietary regimens followed by induction of renal IRI by clamping both the renal pedicles for 37 min. Kidneys were harvested 6hrs and 24hrs (t=6 and 24hrs) post-reperfusion. Results. The pro-inflammatory cytokine TNF-α that plays an important role in induction of IRI was measured by rtPCR and the levels were found to be ameliorated in both the DR and FA groups. FA predominantly results in a very early recruitment of CD3+ T cells as evidenced by increased T cells at t=0hrs in FA animals. As shown by histology and rtPCR at t=6hrs significantly less CD3+ T cells were found in DR and FA animals. rtPCRshowed that γδ T cells were strongly upregulated in FA animals at t=0hrs while at later time points these cells were found to be less frequent. The γδ T cells in AL animals were upregulated at t=6 and 24hrs. One of the most important transcription factors, RORγ, which induces the production of IL-17 in γδ T cells was also found to be an early effector cell in renal IRI. The RORγ expression levels were found to be higher in DR (t=6hrs) and FA groups (t=0hrs). 

Conclusion. Dietary interventions cause major changes in the unconventional T cells. We have shown that DR and FA cause amelioration of renal IRI as the production of TNF-α is found to be less, which is in accordance with survival data. We have also shown that DR and FA cause pre-activation of the CD3+ T cells (mainly γδ T cells), which then cannot be activated and recruited after IRI and which may lead to ameliorated damage. Since DR and FA are a kind of stress, what is evident from RORγ+ γδ T cells is that DR and FA pre-activate this antigen unspecific, first linear responder T cells and therefore (after reperfusion) does not cause initiation of IRI anymore.