Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells

Abstract

T cell activation mediates immunity to pathogens. On the flipside, T cells are also involved in pathological immune responses during chronic autoimmune diseases. We recently reported that zinc aspartate, a registered drug with high bioavailability, dose-dependently inhibits T cell activation and Th1/Th2/Th17 cytokine production of stimulated human and mouse T cells. To understand the suppressive effect of zinc on T cell function, we here investigated the influence of zinc aspartate on human T cells focusing on the secretion of immunosuppressive cytokines, induction of apoptosis, and caspase 3/7 activity. To this end, we monitored either freshly stimulated or pre-activated human T cells in the presence of zinc aspartate from 40–140 µM over a period of 72 h. Under both experimental conditions, we observed a dose-dependent suppression of human T cell proliferation. While IL-1ra, latent TGF-β1, and IL-10 were dose-dependently reduced, we, unexpectedly, detected elevated levels of IL-16 upon zinc supplementation. In addition, the number of cells with active caspase 3/7 and, consecutively, the amount of cells undergoing apoptosis, steadily increased at zinc aspartate concentrations exceeding 100 µM. Taken together, our findings suggest that zinc aspartate impairs T cell fitness and might be beneficial for the treatment of T cell-mediated autoimmune diseases.

Ionic mitigation of CD4+ T cell metabolic fitness, Th1 central nervous system autoimmunity and Th2 asthmatic airway inflammation by therapeutic zinc

“…Fig. S1 E) confirming previous findings 25 .

Figure 2 High concentrations of zinc inhibit blast formation, activation, proliferation and the metabolic fitness of CD4 + T cells.

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“…Fig. S1 D) and as reported earlier 25 . In line with the latter, 100 μM zinc had reduced the absolute numbers of viable cells at 24 h to only 94 ± 12% and 150 μM zinc to only 93 ± 28% compared to stimulated but untreated cells (0 μM zinc).…”

“…Zinc has immunomodulatory capacity through its action on innate and adaptive immune cells including T cells. Especially high doses of zinc impair CD4 + T cell activation and proliferation 9 , 15 , 16 , 20 , 25 . In this context, zinc is discussed as additional therapy regimen for autoimmune diseases and allergies including asthma 17 – 19 .…”

“…To this end, we stimulated CD4 + OT-II T cell receptor (TCR) transgenic (tg) T cells with CD3/CD28 in the absence or presence of 100 μM or 150 μM zinc aspartate (UNIZINK) for 24 h followed by bulk RNA sequencing. We decided to use 100 μM and 150 μM zinc aspartate, because at these concentrations T cells start to be functionally compromised as indicated by reduced activation and impaired proliferation in own pilot experiments and based on published studies 25 . Principal component analysis (PCA) revealed that activated CD4+ T cells in the presence of either 100 μM or 150 μM zinc aspartate separated from activated T cells that have not been treated (Fig.…”

Albumin Substitution in Decompensated Liver Cirrhosis: Don’t Forget Zinc

“…Zinc is also important for sensory functions and is essential for the functioning of the immune system [51,56]. As zinc deficiency results in altered numbers and dysfunction of all immune cells [57], individuals with decreased zinc levels have an increased risk for infectious diseases, autoimmune disorders, and cancer [57][58][59]. On the cellular and organismal level, zinc has been shown to have antioxidant, anti-inflammatory, immunomodulatory, and antiapoptotic effects [60].…”