A burst Zinc could be the key for immune-cell recovery

Immune-enhancing properties of zinc are well documented, yet scientists have been unable to comprehend exactly how it functions. In a groundbreaking study recently released in the March 25 edition of the journal Blood - published by Fred Hutchinson Cancer Research Center - researchers from this renowned institution demonstrate two mechanisms in which this vital mineral supports immunity and suggest innovative ways it could be utilized.

By exploring mice, this group of researchers discovered that Zinc is essential for the creation of protective immune cells called T-Lymphocytes and stimulates regeneration within the thymus - a key organ where these cells are generated.

"This study adds to our knowledge of what zinc is actually doing in the immune system and suggests a new therapeutic strategy for improving recovery of the immune system,"

Dr. Jarrod Dudakov

The investigation also revealed that a novel compound evoking zinc's potent effects on this organ is more effective than its natural counterpart in facilitating immune recovery.

Research into zinc's role in immune system recovery is progressing. Dr. Dudakov believed this may be connected to other discoveries regarding the repair process of the immune system, which might eventually lead to therapies that could aid people who have undergone a blood stem cell transplant for a blood cancer or those whose age-related decline has resulted in compromised immunity.

Optimal Zinc and Thymus gland and its vital immune functions

Previously, Dudakov and his team have established the molecular pathways and cellular types that regulate how the immune system's thymus repairs itself after being damaged. Such treatments may improve vaccine efficacy and expedite recovery from stressful situations like chemotherapy, blood stem cell transplantation or radiotherapy exposure.

Dudakov began investigating zinc several years ago when Dr. Lorenzo Iovino, the study's first author and a research associate at Fred Hutch, joined his lab. Believing that low levels of zinc are associated with diminished immune system capacity and a diminutive thymus - where T cells originate - they sought to investigate how supplementation could remediate this condition in mouse models where immune system integrity has been compromised.

Iovino, a prominent blood stem cell transplant physician, previously demonstrated that zinc supplementation could enhance immune recovery in patients undergoing stem-cell transplants for the potentially fatal multiple myeloma condition. Nonetheless, the research did not elucidate why zinc had proved advantageous.

Zinc vital role in T-cell formation and the renewal of thymic tissue

In mice, Iovino and Dudakov observed that thymuses of those deprived of dietary zinc exhibit a notable reduction in size after as little as three weeks on a no-zinc diet. By demonstrating the essentiality of zinc for T-cell maturation, they revealed how deficiencies can significantly impact immunity.

Furthermore, he discovered that zinc deficiency impairs the recovery of T-cell numbers after mice undergoing immune-contaminating treatments reminiscent of those typically administered to patients awaiting a blood stem cell transplant. An abundance of zinc accelerates this process as well as T-cell recovery.

As Iovino said, the study revealed a remarkable consistency of enhanced reconstitution of the thymus and also robust restoration in peripheral blood cell formation after zinc supplementation; yet still no one could ascertain which mechanism it was operating through.

Iovino discovered that it was the alteration in zinc concentrations around cells that discharge a critical regenerative factor, triggering the thymus' renewal processes. T cells accumulate zinc as they mature but subsequently unleash it after sustaining an adversive event - like exposure to a burst of radiation - which results in their demise.

Cells utilize the GPR39 receptor to detect a change in external zinc levels, and Iovino's investigations have revealed that an experimental compound that mimics an increase in external zinc by stimulating this receptor can also trigger thymic regeneration and renewal factor release.

"What we think is going on is, as you give zinc supplementation, that gets accumulated within the developing T cells. It gets stored and stored and stored, then the damage comes along and the zinc is released, ... Now you have more zinc than you normally would, and it can instigate this regenerative pathway. With the experimental compound we can just directly target GPR39 and basically get the same effect without any of that pre-treatment"

Dr. Jarrod Dudakov

From lab test to clinic

Though advancements are being made, a lot remains to be understood before they can effectively apply their findings into therapeutic approaches.

Patients who undergo a blood stem cell transplant already have their mineral supplements topped up, so if extra zinc were to be included in any treatment regimen, it would need to be verified that individuals receiving it truly require this nutrient.

The GPR39-stimulating compounds are being evaluated as potential therapies to improve thymic recovery after acute injuries such as pre-transplant radiation. Thus far, several similar compounds have been screened to identify any that might be more potent. Efforts are currently underway to ascertain whether compounds such as these could help in the regeneration of thymic tissue. Unfortunately, our T-cell output decreases with age; necessitating an investigation into whether chronic degeneration of this organ can be halted by potentiating its regenerative processes.

Source: ScienceDaily