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Therapeutic effects of recombinant Salmonella typhimurium harboring CCL22 miRNA on atopic dermatitis-like skin in mice

机译:携带CCL22 miRNA的鼠伤寒沙门氏菌重组株对小鼠特应性皮炎样皮肤的治疗作用

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摘要

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-γ 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.
机译:已知Th-2-偏向的免疫反应在特应性皮炎的发病机理中起关键作用。特别地,源自巨噬细胞的趋化因子CCL22直接与Th-2相关的皮肤炎症反应有关,并且其水平在血清中显着升高并且与特应性皮炎中的疾病严重性相关。在这项研究中,我们测试了使用表达miRNA的细菌治疗特应性皮炎的遗传疗法的发展。我们构建了表达CCL22 miRNA(ST-miRCCL22)的鼠伤寒沙门氏菌的重组菌株,用于体内敲除CCL22。 CCL22基因在活化的淋巴细胞中被CCL22 miRNA下调。在患有类似于特应性皮炎的皮肤疾病的小鼠中,用ST-miRCCL22处理后,白细胞介素-4被抑制,干扰素-γ被诱导。此外,在用ST-miRCCL22治疗的特应性小鼠中CCL22水平被抑制。这些结果表明ST-miRCCL22可能是治疗特应性皮炎的有效遗传剂。

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