Rapamycin-Fortified Diet Delays Wound Repair, Alters CD4+ & γδ+ Splenocyte, CD3+ Thymocyte Distributions in Mice

Rapamycin is an immunosuppressant that inhibits mTOR; an important sensor of nutrient availability and a major regulator of a cell’s metabolism and protein synthesis. Prolonged mTOR inhibition with dietary rapamycin extends the life-span of healthy mice to ages greater than those not receiving the drug. However, side effects such as problems with tissue repair have been reported by patients receiving rapamycin in the transplant setting. Given its potential applications in humans, the purpose of this study is to determine whether prolonged dietary rapamycin immunosuppression has negative impacts on immune cell number and function. Mice were placed on either a normal chow diet or an identical diet fortified with rapamycin, for ten weeks. Previously, we showed that short term i.p. injection of rapamycin impaired skin T cell function in wound repair. Here we also found that prolonged dietary rapamycin reduced the ability of biopsy wounds to close. Rapamycin-fed mice exhibited an increase in splenic gd T cells and a reduction in splenic CD4+ T cells, but rapamycin had no significant effect on T cells expressing CD3+, CD8+, or on stimulated gd and CD4+ T cell production of IL-4, IFN-g, or IL-17. Splenic NK, NKT, and B cell percentages were also unaffected by rapamycin. Thymic CD3+ and CD4+ T cells were significantly reduced in rapamycin-fed mice, but rapamycin had no significant effect on thymic gd, double positive (DP; CD4+/CD8+), or double negative (DN; CD4-/CD8-) T cells at any DN developmental stage (DN-1 through DN-4). Our results suggest that diets fortified with 14 ppm rapamycin are sufficient to modulate wound repair capabilities without dramatically altering immune cell development.