Modulation of the development of human monocyte‐derived dendritic cells by lithium chloride |
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| Authors: | Yi‐Yuan Yang Neng‐Yao Shih Chia‐Chen Ho Yu‐Chen Wu Tze‐Sing Huang Ming‐Chyi Huang Hsing‐Cheng Liu Winston W Shen Sy‐Jye Leu |
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| Institution: | 1. School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan;2. Department of Laboratory Medicine, Taipei Medical University‐Wan Fang Hospital, Taipei, Taiwan;3. Graduate Institute of Medical Science, Taipei Medical University, Taipei, Taiwan;4. Center for Reproductive Medicine and Sciences, Taipei Medical University Hospital, Taipei, Taiwan;5. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan;6. Graduate Institute of Cell and Molecular Biology, Taipei Medical University, Taipei, Taiwan;7. Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan;8. Department of Psychiatry, School of Medicine, Taipei Medical University, Taipei, Taiwan;9. Department of Psychiatry, School of Medicine and Taipei Medical University‐Wan Fang Hospital, Taipei, Taiwan;10. Department of Microbiology and Immunology, Taipei Medical University, Taipei, Taiwan |
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| Abstract: | Lithium has been used or explored to treat psychiatric and neurodegenerative diseases that are frequently associated with an abnormal immune status. It is likely that lithium may work through modulation of immune responses in these patients. Because dendritic cells (DC) play a central role in regulating immune responses, this study investigated the influence of lithium chloride (LiCl) on the development and function of DC. Exposure to LiCl during the differentiation of human monocyte‐derived immature DCs (iDC) enhances CD86 and CD83 expression and increases the production of IL‐1β, IL‐6, IL‐8, IL‐10, and TNF‐α. However, the presence of LiCl during LPS‐induced maturation of iDC has the opposite effect. During iDC differentiation, LiCl suppresses the activity of glycogen synthase kinase (GSK)‐3β, and activates PI3K and MEK. In addition, LiCl activates peroxisome proliferator‐activated receptor γ (PPARγ) during iDC differentiation, a pathway not described before. Each of these signaling pathways appears to have distinct impact on the differentiating iDC. The enhanced CD86 expression by LiCl involves the PI3K/AKT and GSK‐3β pathway. LiCl modulates the expression of CD83 in iDC mainly through MEK/ERK, PI3K/AKT, and PPARγ pathways, while the increased production of IL‐1β and TNF‐α mainly involves the MEK/ERK pathway. The effect of LiCl on IL‐6/IL‐8/IL‐10 secretion in iDC is mediated through inhibition of GSK‐3β. We have also demonstrated that PPARγ is downstream of GSK‐3β and is responsible for the LiCl‐mediated modulation of CD86/83 and CD1 expression, but not IL‐6/8/10 secretion. The combined influence of these molecular signaling pathways may account for certain clinical effect of lithium. J. Cell. Physiol. 226: 424–433, 2011. © 2010 Wiley‐Liss, Inc. |
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