Hypothyroidism-related zinc deficiency leads to suppression of T lymphocyte activity
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ORIGINAL ARTICLE
Hypothyroidism-related zinc deficiency leads to suppression of T lymphocyte activity María Alejandra Paulazo1 Alicia Juana Klecha1,2 Helena Andrea Sterle1 Eduardo Valli1 Horacio Torti2 Florencia Cayrol1 María Laura Barreiro Arcos1 Graciela Alicia Cremaschi 1,2 ●
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Received: 20 February 2019 / Accepted: 11 April 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Purpose 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. Methods 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. Results 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. Conclusions 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. Keywords Hypothyroidism Zinc Thyroid hormones T lymphocytes ●
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Introduction These authors contributed equally: María Alejandra Paulazo, Alicia Juana Klecha Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-019-01936-7) contains supplementary material, which is available to authorized users. * Graciela Alicia Cremaschi [email protected] [email protected] 1
Instituto de Investigaciones Biomédicas (BIOMED), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Av. Alicia Moreau de Justo 1600, 3er piso (1107 AAZ), Buenos Aires, Argentina
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Cátedra de Física, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
Immunity is modulated by a complex network of immune and neuroendocrine factors, which, in
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