Hypothyroidism-related zinc deficiency leads to suppression of T lymphocyte activity
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Hypothyroidism has been shown to induce immunosuppression and both the thyroid status and immunity are affected by zinc deficiency. However, the impact of hypothyroidism on zinc metabolism and its possible relationship with the immune status has not yet been deeply explored. Here, our aim was to study whether hypothyroidism may alter zinc metabolism and thus lead to the impairment of T lymphocyte activity.
Variations in the distribution of zinc in the body were evaluated in PTU-treated hypothyroid mice. The effects of hypothyroidism and zinc deficiency were studied on T lymphocyte proliferation after stimulation both in vitro and in vivo. For in vitro assays, thyroid hormone-free or zinc chelator (TPEN or DTPA)-supplemented media were used. For in vivo assays, lymphocyte activity was evaluated in cells from hypothyroid, T3-treated, and zinc-supplemented mice.
Hypothyroid mice showed lower levels of zinc in femur and lymph nodes than controls. T3 and zinc supplementation reversed these effects. In vitro, both thyroid hormone and zinc deficiency led to a decreased response to mitogen stimulation. However, only zinc deficiency was able to induce lymphocyte apoptosis. Mitogen-stimulated T cells from hypothyroid mice showed impaired proliferation, accompanied by decreased activation of PKC and lower levels of p-ERK, effects that were reversed by T3 replacement or zinc supplementation.
Our results show an important role of zinc deficiency in hypothyroid-mediated T-cell suppression and suggest the importance of evaluating zinc levels and restoring them when necessary to maintain an efficient immune response in hypothyroid patients.
KeywordsHypothyroidism Zinc Thyroid hormones T lymphocytes
This work was supported by the National Research Council of Argentina (PIP-CONICET 00275), the University of Buenos Aires (UBACYT 20020130100289BA), the National Agency for Science and Technology (ANPCYT, PICT 2015–0874)
This study was funded by the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) Argentina, PIP-CONICET 00275; the Universidad de Buenos Aires, UBACYT 20020130100289BA and the Fondo para la Investigación Científica y Tecnológica (FONCYT) PICT 2015-0874.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All studies using animals were performed in accordance with the ARRIVE Guidelines  and all the experimental protocols were approved by the Institutional Committee for the Care and Use of Laboratory Animals (CICUAL) of the School of Pharmacy and Biochemistry of the University of Buenos Aires and the CICUAL of BIOMED. This article does not contain any studies with human participants performed by any of the authors.
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