Abstract
Th-2-biased immune responses are known to play a key role in the pathogenesis of atopic dermatitis. In particular, the macrophage-derived chemokine CCL22 is directly implicated in Th-2-associated skin inflammatory reactions, and its levels are significantly elevated in serum and are correlated with disease severity in atopic dermatitis. In this study, we tested the development of genetic therapeutic options to treat atopic dermatitis using bacteria expressing miRNA. We constructed a recombinant strain of Salmonella typhimurium expressing CCL22 miRNA (ST-miRCCL22) for the in vivo knockdown of CCL22. The CCL22 gene was downregulated with CCL22 miRNA in activated lymphocytes. In mice with a cutaneous disease similar to atopic dermatitis, interleukin-4 was inhibited and interferon-g was induced after treatments with ST-miRCCL22. Furthermore, CCL22 levels were suppressed in the atopic mice treated with ST-miRCCL22. These results suggest that ST-miRCCL22 may be an effective genetic agent for treating atopic dermatitis.
Highlights
Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease with recurrent inflammatory episodes that results from a combination of genetic predisposition, imbalanced immune responses, epidermal barrier abnormalities and severe pruritus (Chen et al, 2004)
Raw 264.7 cells were transfected with miRCCL22. miRNA expression in the cell was detected with fluorescence microscopy (× 200) after transfection for 48 hours (Figure 1B)
These data show that the miRNA expression vector in S. typhimurium can be expressed in mammalian cells
Summary
Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease with recurrent inflammatory episodes that results from a combination of genetic predisposition, imbalanced immune responses, epidermal barrier abnormalities and severe pruritus (Chen et al, 2004). Imbalances between the Th-1 and Th-2 immune responses (Th-2-biased immune response) are known to be key factors in the pathogenesis of AD (Akkoc et al, 2008). These two types of helper T-cell responses differ in their functional effects and cytokine production. Cytokines regulate the function of T cells in allergic immune responses. The humoral immune response is dominated by enhanced IgE secretion. In allergic diseases such as AD, Th-2 responses are considered to play primary roles in inducing disease (Yanai et al, 2007)
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