Blood: Zinc promotes regeneration and recovery of the immune system after bone marrow transplantation

For cancer patients, whether they receive chemotherapy, bone marrow transplants, or cell therapy, they face prolonged symptoms of lymphopenia, which puts them at risk of infection and cancer recurrence

The thymus is the main site of T lymphocyte development, and the recovery of T cells depends on the regeneration of thymus tissue, but the repair and regeneration capacity of the thymus decreases with age

Zinc (Zinc) is recognized as a trace element that enhances human immunity.

Recently, Jarrod Dudakov of the Fred Hutchinson Cancer Research Center in the United States published a research paper entitled: Activation of the Zinc-sensing receptor GPR39 promotes T cell reconstitution after hematopoietic cell transplant in mice in the journal Blood

The study found that zinc is essential for normal T cell development and repair after injury, and also promotes T cell generation by promoting thymic regeneration

Zinc supplementation through diet can promote thymus regeneration and functional recovery in mice after hematopoietic stem cell transplantation.

Overall, this study adds to our understanding of the actual role of zinc in the immune system, defines a new pathway for tissue regeneration, and also provides an innovative approach to promote immune system reconstitution in patients following hematopoietic stem cell transplantation

Previously, Jarrod Dudakov's team had investigated the molecular mechanisms and cell types that regulate the self-repair of the immune system's thymus

Previous studies have shown that low levels of zinc are associated with decreased T cells and atrophy of the thymus

Zinc is essential for T cell development and thymus regeneration

In this latest study, the research team found that after just three weeks of a zinc-free diet, the thymus glands of mice shrank and the production of mature T cells was significantly reduced.

Based on the above findings, the research team concluded that after zinc supplementation, the dangerous was better reconstituted, and the T cells in the peripheral blood were also better reconstituted

The research team further found that when a destructive event occurs (such as radiotherapy, myeloablation before hematopoietic stem cell transplantation), thymocytes release previously accumulated zinc, and the cell surface receptor GPR39 senses changes in extracellular zinc levels and stimulates endothelial cells.

Zinc, which is normally ingested through the diet, accumulates and stores in thymocytes and developing T cells, and in the event of a damaging event, zinc from these cells is released extracellularly, leading to elevated levels of extracellular zinc, the team said.

Directly targeting and activating GPR39 through small molecule agonists can immediately initiate thymic tissue regeneration and promote T cell reconstruction, which is better than dietary zinc supplementation

clinical translation

Cancer patients undergoing hematopoietic stem cell transplants, who have received mineral supplements, should first determine if they are truly zinc deficient if adding additional zinc to their treatment regimen

Therefore, they are developing a method to determine whether a patient is zinc deficient, and will be used to confirm whether a patient's zinc status is associated with immune system recovery after hematopoietic stem cell transplantation
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They are also screening for compounds that stimulate GPR39 to promote thymic regeneration and immune system reconstitution after treatment
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In addition, as people age, the thymus gradually shrinks and reduces T cell output, and this research also holds promise for slowing age-related degeneration of the immune system
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foods high in zinc

Original source:

Lorenzo Iovino, Kirsten Cooper, Paul deRoos, et al.
Activation of the Zinc-sensing receptor GPR39 promotes T cell reconstitution after hematopoietic cell transplant in mice .
Blood, 2021013950.