Induction of regulatory T cells in Th1-/Th17-driven experimental autoimmune encephalomyelitis by zinc administration

Rosenkranz, Eva; Maywald, Martina; Hilgers, Ralf-Dieter; Brieger, Anne; Clarner, Tim; Kipp, Markus; Plümäkers, Birgit; Meyer, Sören; Schwerdtle, Tanja; Rink, Lothar

doi:10.1016/j.jnutbio.2015.11.010

Cited by 73 publications

(53 citation statements)

References 61 publications

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“…This shows how both zinc deficiency and increased zinc levels influence T-cell function. Additionally, regulatory T cells (Treg) are induced and stabilized in zinc-supplemented lymphocyte culture (MLC), in lymphocytes from patients allergic to pollen [83] and in experimental autoimmune encephalomyelitis (EAE) [84]. Furthermore, zinc enhances the capacity of TGFβ1 to induce Treg cells [85,86].…”

Section: Zinc Status and Inflammatory Cytokinesmentioning

confidence: 99%

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Zinc in Infection and Inflammation

Gammoh¹,

Rink²

2017

Preprint

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126

139

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Abstract:Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors or differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B, a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

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Section: Zinc Status and Inflammatory Cytokinesmentioning

confidence: 99%

“…However, the capacity of zinc to induce Tregs is dependent on the activation status of the cells. Activated zinc-supplemented T cells are driven to differentiate to Treg, whereas resting T cells are pushed to TH1 response [84]. Hence, the influence of zinc is expansive yet specific to each cell type.…”

Section: Zinc Status and Inflammatory Cytokinesmentioning

confidence: 99%

Zinc in Infection and Inflammation

Gammoh¹,

Rink²

2017

Preprint

Self Cite

126

139

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“…Several reports indicate that Zn treatment prevents T-cell-mediated immune responses in vivo and in vitro [78, 164–166] and enhances the number and activity of Tregs in some cases [156, 167, 168]. In vitro , Zn attenuates Th17 differentiation, which is controlled by IL-6-induced STAT3 activation during chronic inflammation by suppressing STAT3 activation [89].…”

Section: Roles Of Zn and Zn Transporters In The Adaptive Immune Symentioning

confidence: 99%

“…In vitro , Zn attenuates Th17 differentiation, which is controlled by IL-6-induced STAT3 activation during chronic inflammation by suppressing STAT3 activation [89]. Reflecting this result, in vivo studies show that moderate Zn treatment inhibits Th17-cell development and disease severity in mice with experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA) [78, 167]. Moreover, at higher concentrations, Zn suppresses T-cell proliferation in mice [169] and cytokine production in human Jurkat [154] and CD4 + T cells [144].…”

Section: Roles Of Zn and Zn Transporters In The Adaptive Immune Symentioning

confidence: 99%

“…Hence, it is not surprising that memory-recall responses to previously encountered antigens are attenuated in ZnD animals [74, 167, 168, 173], since a ZnD or ZIP10-deficient environment considerably attenuates GC formation [27]. These findings suggest that the impaired signaling through BCR in the mature B cells from these mice may be not sufficient to support their differentiation during GC reaction.…”

Section: Roles Of Zn and Zn Transporters In The Adaptive Immune Symentioning

confidence: 99%

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Roles of Zinc Signaling in the Immune System

Hojyo

Fukada

2016

Journal of Immunology Research

209

169

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Zinc (Zn) is an essential micronutrient for basic cell activities such as cell growth, differentiation, and survival. Zn deficiency depresses both innate and adaptive immune responses. However, the precise physiological mechanisms of the Zn-mediated regulation of the immune system have been largely unclear. Zn homeostasis is tightly controlled by the coordinated activity of Zn transporters and metallothioneins, which regulate the transport, distribution, and storage of Zn. There is growing evidence that Zn behaves like a signaling molecule, facilitating the transduction of a variety of signaling cascades in response to extracellular stimuli. In this review, we highlight the emerging functional roles of Zn and Zn transporters in immunity, focusing on how crosstalk between Zn and immune-related signaling guides the normal development and function of immune cells.

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