4.5 Article

Rapamycin delays allograft rejection in obese graft recipients through induction of myeloid-derived suppressor cells

期刊

IMMUNOLOGY LETTERS
卷 236, 期 -, 页码 1-11

出版社

ELSEVIER
DOI: 10.1016/j.imlet.2021.05.003

关键词

Rapamycin; Obesity; Transplantation; MDSCs; T cells

资金

  1. University of Tubingen [2461-0-0, 2458-0-0, 2606-0-0]
  2. IZKF Promotionskolleg program of the University of Tubingen [2018-2]

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The study found that rapamycin delayed allograft rejection in obese graft recipients by enhancing suppressive immune cell function and shifting immune cell subsets towards anti-inflammatory conditions.
Obesity has become a relevant problem in transplantation medicine with steadily increasing numbers of obese graft recipients. However, the effect of immunomodulatory drugs on transplant-related outcomes among obese patients are unknown. Therefore, we evaluated the impact of rapamycin on allograft rejection and alloimmune response in a murine model of diet-induced obesity and fully-mismatched skin transplantation. Rapamycin significantly delayed allograft rejection in obese recipient mice compared to treated lean mice (14.5 days vs. 10.7 days, p = 0.005). Treatment with rapamycin increased frequencies of monocytic myeloid-derived suppressor cells (M-MDSCs), augmented the immunosuppressive activity of M-MDSCs on T cells through indoleamine 2,3-dioxygenase pathway and shifted CD4(+) T cells towards regulatory T cells in obese graft recipients. In summary, our results demonstrate that rapamycin delays allograft rejection in obese graft recipients by enhancing suppressive immune cell function and shifting immune cell subsets towards anti-inflammatory conditions.

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