NIV Congres

Background Seventy-two hours of preoperative fasting (F) 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. Adaptive immunity, especially the B and T lymphocytes, has been shown to play a crucial role in the pathophysiology of IRI. Therefore, we investigated the impact of fasting and dietary restriction on B and T cells in the various lymphoid organs.

Materials and Methods Male C57Bl/6 mice were fed ad libitum (AL) or underwent 72 hours F or 30% DR for 2  weeks (n=8/group). Consequently, the mice were sacrificed and bone marrow (BM), thymus, spleen and mesenteric lymph nodes (mLN) were harvested and processed into cell suspensions. These cells were stained with B and T cell markers for FACS analysis such as CD19, B220, CD3, CD4, CD8 etc. These stained cells were then phenotypically analysed on a LSRII flow cytometer.

Results Both DR and F cause significant (p≤0.05) depletion in the early immature B cell development and a significant increase in recirculating mature B cells (p≤0.05) in the BM as compared to that of the AL group. The splenic CD19⁺B220⁺ B cell population was significantly decreased (p≤0.001) in the F group while no changes were observed in the DR group when compared with AL. Other B cell subsets showed a decrease of all subtypes such as IgMlowIgDlow, IgM⁺IgD^- as well as IgM⁺IgD⁺ subsets in the F group (p≤0.05). Significant downregulation in marginal as well as follicular zone B cells was also observed in spleen with again a pronounced effect due to F (p≤0.005). The same trend was also observed in mLN. CD3⁺T cells in BM, spleen and mLN were significantly increased in F group (p≤0.05) as compared to that of AL and DR group while the T cell development in thymus was arrested at the early DN2 stage and ISP stage (p≤0.05), hence causing confinement of the T cell development and maturation.

Conclusion Dietary interventions cause alternations in all the lymphoid compartments. Compared to DR, F has a more pronounced effect. We conclude that DR and F arrest B and T cell development and also cause recruitment of both recirculating mature B cells and T cells to the BM. These alterations in the lymphoid compartments may be one of the mechanisms by which dietary interventions protect against renal IRI, but further investigation into this is required.