T-Lymphocytes: A Target for Stimulatory and Inhibitory Effects of Zinc Ions | BenthamScience

T-Lymphocytes: A Target for Stimulatory and Inhibitory Effects of Zinc Ions

Author(s): Andrea Honscheid, Lothar Rink, Hajo Haase.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets

Volume 9 , Issue 2 , 2009

Abstract:

The trace element zinc is a crucial cofactor for many proteins involved in cellular processes like differentiation, proliferation and apoptosis. Zinc homeostasis is tightly regulated and disturbance of this homeostasis due to genetic defects, zinc deficiency, or supplementation influences the development and the progression of various infectious and autoimmune diseases. The immune system is strongly impaired during zinc deficiency, predominantly the cell-mediated response by T-lymphocytes. During zinc deprivation T-lymphocyte development, polarization into effector cells, and function are impaired. This leads to reduced T-cell numbers, a decreased ratio of type 1 to type 2 T-helper cells with reduced production of T-helper type 1 cytokines like interferon-gamma, and compromised T-cell mediated immune defense. Accordingly, disturbed zinc homeostasis increases the risk for infections, and zinc supplementation restores normal immune function. Furthermore, several disorders, like mycobacterial infections, asthma, diabetes, and rheumatoid arthritis are accompanied by decreased zinc levels and in some cases disease progression can be affected by zinc supplementation. On the molecular level, apoptosis of T-cell precursors is influenced by zinc via the Bcl-2/Bax ratio, and zinc ions inhibit caspases-3, -6, -7, and -8. In mature T-cells, zinc interacts with kinases involved in T-cell activation, like protein kinase C and the lymphocyte protein tyrosine kinase (Lck), while higher zinc concentrations are inhibitory, reducing the activities of the interleukin-1 receptor-associated kinase (IRAK) and calcineurin. Taken together, zinc homeostasis influences Tlymphocytes via several molecular targets, leading to a modulation of T-cell-dependent immune responses.

Keywords: T-lymphocytes, zinc, zinc deficiency, signal transduction, immune system

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Article Details

VOLUME: 9
ISSUE: 2
Year: 2009
Page: [132 - 144]
Pages: 13
DOI: 10.2174/187153009788452390
Price: $58

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