title: Zinc deficiency adversely influences interleukin-4 and interleukin-6 signaling.
abstract: Zinc deficiency is accompanied by a severe impairment of the immune system, causing a high risk for infections and autoimmune diseases due to altered functionality of B- and T- cells. The influence of zinc deficiency on T- and B- cells via alteration of cytokine expression is well established. The aim of this study was to examine potential direct effects of zinc deficiency on the reactivity of B- and T- cells. Zinc deficient B- and T- cells revealed divergent reaction patterns compared to zinc sufficienT-cells. This was manifested by a stronger proliferative response following IL-6 and IL-2 stimulation on the one hand, but less proliferation following IL-4 stimulation on the other hand. Moreover, these results were supported by the finding that the B- and T-cell signaling cascades activated by IL-4 or IL-6, respectively, were affected directly by zinc deficiency, resulting in reduced Stat6 phosphorylation and increased Stat3 phosphorylation. Whereas the transcription factor Stat6 is involved in IL-4 signaling, Stat3 is activated by IL-6 signaling. Consequently, these results show opposing effects of zinc deficiency on IL-4 and IL-6/IL-2 signaling pathways, thus underlying the importance of zinc for proper immune function.
authors.affiliation: Institute of Immunology, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Gruber
authors.forename: M
authors.initials: M
authors.lastname: Maywald
authors.forename: E
authors.initials: E
authors.lastname: Rosenkranz
authors.forename: H
authors.initials: H
authors.lastname: Haase
authors.forename: B
authors.initials: B
authors.lastname: Plumakers
authors.forename: L
authors.initials: L
authors.lastname: Rink
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015032:Zinc / Q000172:deficiency*
chemical_list: D007376:Interleukin-2; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D050800:STAT6 Transcription Factor; C494087:Stat3 protein, mouse; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D015032:Zinc