Iovino L, deRoos P, Kinsella S, et al. Activation of the Zinc-Sensing Receptor GPR39 Promotes T Cell Reconstitution After Hematopoietic Cell Transplant in Mice. Blood. 2022; (doi: 10.1182/blood.2021013950).
Whether released naturally in the body or introduced via dietary supplementation, mouse studies show that zinc promotes T cell reconstitution in the setting of hematopoietic stem cell transplant (HSCT). Lymphopenia is a serious and common problem linked to HCT, with no currently approved intervention. Zinc might be a viable treatment, suggest researchers, who note that it promotes normal T cell development in the thymus as well as epithelial repair following severe damage. After HCT conditioning, zinc built up in thymocytes during development is released into the extracellular milieu, where the cell surface receptor GPR39 detects it and starts regeneration. After transplant surgery, based on results from a murine model of allogeneic HSCT, dietary intake of zinc has the effect of targeting GPR39 directly to stimulate thymic function even in the absence of prior zinc accumulation in thymocytes. These findings suggest an innovative preclinical approach to treat lymphopenia in HCT recipients that can be further explored.