Sakari Kauppinen

Publications (2)12.71 Total impact

• Article: MiR-21 is up-regulated in psoriasis and suppresses T cell apoptosis.

  Florian Meisgen, Ning Xu, Tianling Wei, Peter C Janson, Susanna Obad, Oliver Broom, Nikoletta Nagy, Sakari Kauppinen, Lajos Kemény, Mona Ståhle, Andor Pivarcsi, Enikö Sonkoly
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  ABSTRACT: MicroRNAs are short non-coding RNAs that regulate gene expression. Previously, in a genome-wide screen, we found deregulation of microRNA expression in psoriasis skin. MicroRNA-21 (miR-21) is one of the microRNAs significantly up-regulated in psoriasis skin lesions. To identify the cell type responsible for the increased miR-21 level, we compared expression of miR-21 in epidermal cells and dermal T cells between psoriasis and healthy skin and found elevated levels of miR-21 in psoriasis in both cell types. In cultured T cells, expression of miR-21 increased markedly upon activation. To explore the function of miR-21 in primary human T helper cells, we inhibited miR-21 using a tiny seed-targeting LNA-anti-miR. Specific inhibition of miR-21 increased the apoptosis rate of activated T cells. Our results suggest that miR-21 suppresses apoptosis in activated T cells, and thus, overexpression of miR-21 may contribute to T cell-derived psoriatic skin inflammation.
  Experimental Dermatology 04/2012; 21(4):312-4. · 3.54 Impact Factor
• Article: MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte-associated antigen 4.

  Enikö Sonkoly, Peter Janson, Marja-Leena Majuri, Terhi Savinko, Nanna Fyhrquist, Liv Eidsmo, Ning Xu, Florian Meisgen, Tianling Wei, Maria Bradley, Jan Stenvang, Sakari Kauppinen, Harri Alenius, Antti Lauerma, Bernhard Homey, Ola Winqvist, Mona Ståhle, Andor Pivarcsi
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  ABSTRACT: 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. We sought to explore the role of miRNAs in the pathogenesis of atopic dermatitis. 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. 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. miR-155 is significantly overexpressed in patients with atopic dermatitis and might contribute to chronic skin inflammation by increasing the proliferative response of T(H) cells through the downregulation of CTLA-4.
  The Journal of allergy and clinical immunology 09/2010; 126(3):581-9.e1-20. · 9.17 Impact Factor