4.5 Article

Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction

Journal

JOURNAL OF LEUKOCYTE BIOLOGY
Volume 78, Issue 1, Pages 135-143

Publisher

WILEY
DOI: 10.1189/jlb.0804477

Keywords

lymphocytes; neuroinflammation; neurodegeneration

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Minocycline, a tetracycline with antiinflammatory properties, has been reported to down-regulate the activity of microglia, whose activation occurs in inflammatory and degenerative diseases of the central nervous system, such as multiple sclerosis and Alzheimer's disease. In these disorders, a T cell component is also evident, and we have demonstrated previously that the interaction of activated T cells with microglia led to the substantial increase in tumor necrosis factor alpha (TNF-alpha) levels. Here, we report that minocycline decreases TNF-alpha levels produced in human T cell-microglia interaction. This effect is mediated by a direct action of minocycline on the activated T cells and on microglia, which resulted in the decreased ability of T cells to contact microglia. In correspondence, minocycline decreased the expression on T cells of the CD40 ligand (CD40L), a key molecule regulating the contact-mediated interaction of T cells with microglia. These results demonstrate that the mechanism of action of minocycline involves not only microglia but also T cells and their subsequent activation of microglia. The capacity of minocycline to down-regulate CD40L on T cells may provide a new means to target the CD40m-CD40L pathway, which regulates several inflammatory processes.

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