Abstract
Background & aims: The micronutrient zinc is essential for proper immune function. Consequently, zinc deficiency leads to impaired immune function, as seen in decreased secretion of interleukin (IL)-2 by T cells. Although this association has been known since the late 1980s, the underlying molecular mechanisms are still unknown. Zinc deficiency and reduced IL-2 levels are especially found in the elderly, which in turn are prone to chronic diseases. Here, we describe a new molecular link between zinc deficiency and reduced IL-2 expression in T cells. Methods: The effects of zinc deficiency were first investigated in vitro in the human T cell lines Jurkat and Hut-78 and complemented by in vivo data from zinc-supplemented pigs. A short- and long-term model for zinc deficiency was established. Zinc levels were detected by flow cytometry and expression profiles were investigated on the mRNA and protein level. Results: The expression of the transcription factor cAMP-responsive-element modulator α (CREMα) is increased during zinc deficiency in vitro, due to increased protein phosphatase 2A (PP2A) activity, resulting in decreased IL-2 production. Additionally, zinc supplementation in vivo reduced CREMα levels causing increased IL-2 expression. On epigenetic levels increased CREMα binding to the IL-2 promoter is mediated by histone deacetylase 1 (HDAC1). The HDAC1 activity is inhibited by zinc. Moreover, deacetylation of the activating histone mark H3K9 was increased under zinc deficiency, resulting in reduced IL-2 expression. Conclusions: With the transcription factor CREMα a molecular link was uncovered, connecting zinc deficiency with reduced IL-2 production due to enhanced PP2A and HDAC1 activity.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Clinical Nutrition |
| Vol/bind | 40 |
| Nummer | 5 |
| Sider (fra-til) | 3263-3278 |
| Antal sider | 16 |
| ISSN | 0261-5614 |
| DOI | |
| Status | Udgivet - maj 2021 |