MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated antigen 4

TY - JOUR

T1 - MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated antigen 4

AU - Sonkoly , Enikö

AU - Janson , Peter

AU - Majuri , Marja-Leena

AU - Savinko , Terhi

AU - Fyhrquist , Nanna

AU - Eidsmo , Liv

AU - Xu , Ning

AU - Meisgen , Florian

AU - Wei , Tianling

AU - Bradley , Maria

AU - Stenvang, Jan

AU - Kauppinen , Sakari

AU - Alenius, Harri

AU - Lauerma , Antti

AU - Homey , Bernard

AU - Winqvist , Ola

AU - Ståhle , Mona

AU - Pivarcsi , Andor

PY - 2010/9

Y1 - 2010/9

N2 - 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 TH 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 TH 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.

AB - 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 TH 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 TH 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.

U2 - 10.1016/j.jaci.2010.05.045

DO - 10.1016/j.jaci.2010.05.045

M3 - Journal article

C2 - 20673989

SN - 0091-6749

VL - 126

SP - 581-589.e20

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 3

ER -