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Critical Reviews™ in Immunology
Structure of IL-10 and Its Role in Autoimmune Exocrinopathy
Department of Pathology, Tokushima University School of Dentistry, 3-18-15, Kuramotocho, Tokushima 770-8504, Japan
Cytokines are implicated in the pathogenesis of a variety of autoimmune disorders. Whether the presence of cytokines is primary or secondary and the extent to which these factors may contribute to the development and progression of clinicopathologic alterations in these disorders remain largely unknown but are highly important questions. Our research focuses on evaluating these issues by using a transgenic approach to direct the constitutive expression of cytokines to epithelial cells in the intact exocrine glands of mice. Our recent studies have focused on the potential of the regulatory cytokine IL-10 produced by type 2 T-helper cells to inhibit inflammation and the development of autoimmue diseases. Using targeted introduction of this molecule into the exocrine gland epithelial cells, we found that IL-10 induced apoptosis of glandular tissues destruction and lymphocyte infiltration consisting primarily of Fas-ligand+ CD4+ T cells, as well as in vitro upregulation of FasL expression on T cells. These results suggest that IL-10 is necessary and sufficient for exocrine gland dysfunction in the transgenic mice. This article discusses recent advances in IL-10 and its role in the pathological conditions of autoimmune exocrinopathy.
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