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Inhibition of interleukin‐1 β ‐mediated interleukin‐1 receptor‐associated kinase 4 phosphorylation by zinc leads to repression of memory T helper type 17 response in humans
Author(s) -
Lee Hyunju,
Kim Bonah,
Choi Yeon Ho,
Hwang Yuri,
Kim Dong Hyun,
Cho Sunjung,
Hong Sung Jun,
Lee WonWoo
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12536
Subject(s) - immune system , biology , extracellular , zinc , microbiology and biotechnology , interleukin , signal transduction , kinase , cytokine , chemistry , immunology , organic chemistry
Summary Zinc is an essential trace element that plays pivotal roles in multiple facets of the immune system. Besides its catalytic and structural roles, zinc also functions as an intracellular signalling molecule, and changes in zinc levels can cause both direct and indirect modulation of immune responses. Further, cytoplasmic levels of bioavailable zinc in immune cells are largely influenced by many extracellular stimuli. Here we provide evidence that zinc represses memory T helper type 17 responses in humans by inhibiting interleukin‐1 β ( IL ‐1 β )‐mediated signal. In vitro zinc treatment of CD 4 + T cells in the presence of activated monocytes inhibited interferon‐ γ ‐producing cells and IL ‐17‐producing cells, but not IL ‐4‐producing cells. Of note, production of IL ‐17 + cells from memory CD 4 + T cells, which is significantly up‐regulated by lipopolysaccharide‐stimulated monocytes, was preferentially repressed by zinc. Increased cytoplasmic zinc in T cells suppressed IL ‐1 β signalling through repression of phosphorylation of IL‐1 receptor‐associated kinase 4 (IRAK4), so leading to an inhibitory effect on T helper type 17 responses facilitated by monocyte‐derived IL ‐1 β in humans. These findings suggest that extracellular zinc bioavailability may affect memory CD 4 + T‐cell responses by modulating the zinc‐mediated signalling pathway.