期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 126, 期 3, 页码 581-U306出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2010.05.045
关键词
Atopic eczema/dermatitis; microRNA; miR-155; cytotoxic T lymphocyte-associated antigen; CD4(+) T-H cells; inflammation
资金
- Swedish Research Council
- Medical Research Council (Vetenskapsradet)
- Welander Finsens Foundation
- Karolinska Institutet
- Tore Nilsons, Hesselman, Konsul ThC Bergh, and Wallenberg Foundations
- [TAMOP-4.2.2/08/1]
Background: MicroRNAs (miRNAs) are short noncoding RNAs that suppress gene expression at the posttranscriptional level. Atopic dermatitis is a common chronic inflammatory skin disease characterized by the presence of activated T cells within the skin. Objective: We sought to explore the role of miRNAs in the pathogenesis of atopic dermatitis. Methods: Global miRNA expression in healthy and lesional skin of patients with atopic dermatitis was compared by using TaqMan MicroRNA Low Density Arrays. miR-155 expression in tissues and cells was quantified by means of quantitative real-time PCR. The cellular localization of miR-155 was analyzed by means of in situ hybridization. The regulation of cytotoxic T lymphocyte-associated antigen (CTLA-4) by miR-155 was investigated by using luciferase reporter assays and flow cytometry. CTLA-4 expression and functional assays were performed on T-H cells overexpressing miR-155. Results: miR-155 was one of the highest-ranked upregulated miRNAs in patients with atopic dermatitis. In the skin miR-155 was predominantly expressed in infiltrating immune cells. miR-155 was upregulated during T-cell differentiation/activation and was markedly induced by T-cell activators in PBMCs in vitro and by superantigens and allergens in the skin in vivo. CTLA-4, an important negative regulator of T-cell activation, was identified as a direct target of miR-155. Overexpression of miR-155 in T-H cells resulted in decreased CTLA-4 levels accompanied by an increased proliferative response. Conclusion: miR-155 is significantly overexpressed in patients with atopic dermatitis and might contribute to chronic skin inflammation by increasing the proliferative response of TH cells through the downregulation of CTLA-4. (J Allergy Clin Immunol 2010; 126: 581-9.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据