• Burst of accumulated zinc shows how the

    From ScienceDaily@1:317/3 to All on Thu Mar 31 22:30:44 2022
    Burst of accumulated zinc shows how the mineral boosts immune function, suggesting ways to improve health
    In mice, zinc helps thymus of the immune system regrow and immune-cell recovery after bone marrow transplant

    Date:
    March 31, 2022
    Source:
    Fred Hutchinson Cancer Research Center
    Summary:
    Zinc's immune-boosting properties are well-established, but
    scientists haven't known exactly how it works. Scientists now
    reveal two ways the mineral supports immunity and suggest how it
    could be used to improve health. Using mice, the team discovered
    that zinc is needed for the development of disease-fighting immune
    cells called T cells and prompts regeneration of the thymus,
    the immune organ that produces T cells.



    FULL STORY ========================================================================== Zinc's immune-boosting properties are well-established, but scientists
    haven't known exactly how it works. In a new study published online
    March 25 in the journal Blood, Fred Hutchinson Cancer Research Center scientists reveal two ways the mineral supports immunity and suggest
    how it could be used to improve health.


    ========================================================================== Using mice, the team discovered that zinc is needed for the development
    of disease-fighting immune cells called T cells and prompts regeneration
    of the thymus, the immune organ that produces T cells.

    "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," said senior author Dr. Jarrod Dudakov,
    an immunologist at Fred Hutch.

    The study also revealed that an experimental compound that mimics
    zinc's action in this organ works even better than the natural mineral
    to promote immune recovery.

    "We are now looking into how zinc may fit in with our other discoveries
    of how the immune system repairs itself and could eventually lead to
    therapies to improve immune function for people who receive a blood stem
    cell transplant for a blood cancer or people with chronic immune decline
    that accompanies aging," Dudakov said.

    Thymic regeneration and immune function, and zinc Previously, Dudakov
    and his team have outlined the molecular pathways and cell types that
    govern how the immune system's thymus repairs itself after injury.

    Such treatments could improve vaccine efficacy and hasten thymic
    regeneration after stressors like chemotherapy, blood stem cell transplant
    and radiation exposure.



    ========================================================================== Dudakov began studying zinc a few years ago when Dr. Lorenzo Iovino,
    the study's first author and a research associate at Fred Hutch, joined Dudakov's lab. Since the scientists knew that low levels of zinc are
    linked to fewer infection fighting T cells and a shrunken thymus, where
    T cells develop, Dudakov and Iovino explored how to supplement with zinc
    in mouse models where the immune system is damaged.

    Iovino, who's also a blood stem cell transplant physician, had shown
    in a previous study that zinc could boost immune recovery in patients undergoing stem-cell transplants for the blood cancer multiple myeloma.

    But the study didn't explain why zinc was helping.

    Zinc is critical for T-cell development and thymic regeneration As in
    humans, Iovino and Dudakov found that the thymuses of mice deprived of
    dietary zinc shrink and produce notably fewer mature T cells, even after
    as little as three weeks of a no-zinc diet. Iovino was able to show that without zinc, T cells cannot fully mature.



    ==========================================================================
    He also found that zinc deficiency slows recovery of T-cell numbers
    after mice receive immune-destroying treatments akin to those given to
    patients about to receive a blood stem cell transplant.

    Conversely, extra zinc speeds this process, and T cells recover faster
    than normal. The team saw a similar result in a mouse model of blood
    stem cell transplant.

    "So we had a consistent result of a better reconstitution of the thymus
    and also a better reconstitution of T cells in the peripheral blood
    after zinc supplementation," Iovino said. "But we still didn't know how
    exactly zinc was working." Iovino discovered that it was the change in
    zinc levels around cells that release a key regenerative factor that
    seemed to kick off the thymus' renewal processes. T cells accumulate
    zinc as they develop, but release it after a damaging event -- like a
    burst of radiation -- kills them off.

    Cells use a molecule called GPR39 to sense a change in external zinc,
    and Iovino found that an experimental compound that mimics rising
    external zinc levels by stimulating GPR39 could also promote renewal
    factor release and thymic regeneration.

    "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," Dudakov said.

    "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 pretreatment." Getting to the clinic There's still a lot to
    learn before they can turn their findings to therapeutic strategies,
    the scientists said.

    Transplant patients already receive mineral supplements, so if
    extra zinc were to be incorporated into their treatment regimens,
    it would be important to make sure that anyone receiving it is truly zinc-deficient. Iovino thinks many patients might be, but right now there
    isn't a good test to assess this. He's currently working on developing
    one, which would first be used to help researchers determine whether
    patients' zinc status correlates with immune recovery after blood stem
    cell transplant.

    Dudakov will pursue GPR39-stimulating compounds as therapies to improve
    thymic recovery after acute injuries like pre-transplant radiation. The
    team is currently screening similar compounds to find any that may be
    more effective.

    He and Iovino are also working to determine whether such compounds
    could help with thymic regeneration in other settings. Unfortunately,
    our thymuses also slowly shrink and reduce their T-cell output as we
    age. Dudakov and Iovino would also like to know whether this chronic degeneration could be slowed by boosting the organ's regenerative
    processes.

    "Our lab is continuing to piece together the molecular players that
    contribute to thymus regrowth," Dudakov said. "Ultimately, we aim to
    develop therapies that trigger natural regeneration and restore immune
    health." The study was funded by the National Institutes of Health,
    the American Society of Hematology and The Rotary Foundation.


    ========================================================================== Story Source: Materials provided by
    Fred_Hutchinson_Cancer_Research_Center. Original written by Sabrina
    Richards. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Lorenzo Iovino, Kirsten Cooper, Paul deRoos, Sinead Kinsella, Cindy
    Anggelica Evandy, Tamas Ugrai, Francesco Mazziotta, Kathleen
    S. Ensbey, David Granadier, Kayla Hopwo, Colton W Smith, Alex
    Gagnon, Sara Galimberti, Mario Petrini, Geoffrey R Hill, Jarrod A
    Dudakov. Activation of the Zinc-sensing receptor GPR39 promotes
    T cell reconstitution after hematopoietic cell transplant in
    mice. Blood, 2022; DOI: 10.1182/ blood.2021013950 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220331185359.htm

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