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

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

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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.

Enhancing the repair and regeneration of the thymus has significant clinical implications for restoring the immune system, but there are currently no approved treatments.

Zinc (Zinc)is a recognized trace element that enhances human immunity. Previous studies have also shown that zinc can promote the recovery of the immune system of cancer patients undergoing stem cell transplantation, but exactly how zinc plays this role is unclear.

Recently, Jarrod Dudakov and others from 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 .

The study further revealed that after hematopoietic stem cell transplantation, zinc accumulated in thymocytes is released into the extracellular environment, and stimulates endothelial cells to produce the regenerative factor BMP4 through the cell surface receptor GPR39 , thereby promoting thymic tissue regeneration.

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

The research team further confirmed that using small molecule agonists to directly target GPR39 can directly enhance thymic regeneration and functional recovery, and the effect is better than supplementation zinc .

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 studied the molecular mechanisms and cell types that regulate the self-repair of the immune system’s thymus.

These studies help improve the effectiveness of vaccines and accelerate thymus regeneration and promote immune system recovery after chemotherapy, cell therapy, radiation exposure, and more.

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

And zinc supplementation boosts immune system recovery in those with multiple myeloma who receive stem cell transplants. But it’s unclear how zinc exerts these effects.

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. 

They also found that in mice with compromised immune systems, zinc deficiency slowed the recovery of T-cell numbers, whereas zinc supplementation accelerated it more than normal. In mice transplanted with hematopoietic stem cells, they observed similar results.

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. But exactly how zinc performs these functions is unclear.

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

The regeneration factor BMP4 is produced, thereby promoting thymic tissue regeneration.

Zinc, 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. , thereby triggering thymic regeneration.

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.

Lorenzo Iovino , lead author of the paper, believes that most patients are zinc deficient, but there are currently no good standards to test for this.

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.

They are also screening for compounds that stimulate GPR39 to promote thymic regeneration and immune system reconstitution after treatment.

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.

foods high in zinc

Reference :
https://doi.org/10.1182/blood.2021013950

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

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