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- W4313373733 abstract "Abstract Hematopoietic stem cell transplant (HSCT) is a well-established therapy with curative potential for a variety of malignant and non-malignant diseases. However, delayed T cell reconstitution is an important contributor to transplant-related morbidity and mortality due to infections and malignant relapse. Optimal T cell development requires a functional thymus and many patients who could benefit from enhancing immune regeneration after HSCT have poor thymic function due to their age or their exposure to chemo- and radiation therapy. Here, we show that zinc, which is the second most abundant trace metal in the body, is crucial for thymic function and can be used to promote T cell reconstitution after HSCT. Mice that had been fed a zinc deficient diet for 3 weeks showed reduced thymic cellularity as zinc was required for the expansion and transition from DN to DP thymocytes. Conversely, supplementation of zinc in drinking water could significantly enhance T cell reconstitution after HSCT. Mechanistically, we found a switch in the bioavailability of zinc following damage, likely due to the death of thymocytes; and its release from thymocytes was able to directly stimulate the zinc-gated receptor GPR39 on endothelial cells to directly induce the production of BMP4; which we have previously identified as a key mediator of endogenous thymic regeneration. Consistent with this hypothesis, mice that had been given a pharmacologic inhibitor of BMP4 signaling did not demonstrate any improved thymic regeneration after zinc supplementation. In conclusion, we have demonstrated that zinc is important for steady-state T cell development and zinc supplementation offers a simple but innovative therapeutic strategy to improve T cell reconstitution." @default.
- W4313373733 created "2023-01-06" @default.
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- W4313373733 date "2020-05-01" @default.
- W4313373733 modified "2023-10-16" @default.
- W4313373733 title "Supplementation of dietary zinc promotes T cell reconstitution after hematopoietic stem cell transplant" @default.
- W4313373733 doi "https://doi.org/10.4049/jimmunol.204.supp.87.29" @default.
- W4313373733 hasPublicationYear "2020" @default.
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