» Articles » PMID: 20673989

MiR-155 is Overexpressed in Patients with Atopic Dermatitis and Modulates T-cell Proliferative Responses by Targeting Cytotoxic T Lymphocyte-associated Antigen 4

Abstract

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 T(H) cells through the downregulation of CTLA-4.

Citing Articles

Resolution of Chronic Inflammation, Restoration of Epigenetic Disturbances and Correction of Dysbiosis as an Adjunctive Approach to the Treatment of Atopic Dermatitis.

Livshits G, Kalinkovich A Cells. 2024; 13(22).

PMID: 39594647 PMC: 11593003. DOI: 10.3390/cells13221899.


An overview on the interaction between non-coding RNAs and CTLA-4 gene in human diseases.

Ebrahimi A, Barati T, Mirzaei Z, Fattahi F, Mansoori Derakhshan S, Shekari Khaniani M Med Oncol. 2024; 42(1):13.

PMID: 39585522 DOI: 10.1007/s12032-024-02552-w.


Immune modulatory microRNAs in tumors, their clinical relevance in diagnosis and therapy.

Vaxevanis C, Bachmann M, Seliger B J Immunother Cancer. 2024; 12(8).

PMID: 39209767 PMC: 11367391. DOI: 10.1136/jitc-2024-009774.


Atopic Dermatitis and Autism Spectrum Disorders: Common Role of Environmental and Clinical Co-Factors in the Onset and Severity of Their Clinical Course.

Casella R, Miniello A, Buta F, Yacoub M, Nettis E, Pioggia G Int J Mol Sci. 2024; 25(16).

PMID: 39201625 PMC: 11354676. DOI: 10.3390/ijms25168936.


The role of microRNAs in atopic dermatitis.

Khosrojerdi M, Jabbari Azad F, Yadegari Y, Ahanchian H, Azimian A Noncoding RNA Res. 2024; 9(4):1033-1039.

PMID: 39022685 PMC: 11254505. DOI: 10.1016/j.ncrna.2024.05.012.