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Age-related decrease of miRNA-92a levels in human CD8+ T-cells correlates with a reduction of na?ve T lymphocytes

DOI: 10.1186/1742-4933-8-11

Keywords: cellular miR-92a, na?ve T lymphocytes, ageing

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Abstract:

MicroRNAs (miRNAs) consist of short noncoding RNA molecules of approximately 18-22 nucleotides that regulate post-transcriptional gene expression by degradation or repression of mRNA molecules. The miR-17-92a cluster is known to be a regulator of the immune system and is critical for lymphoid cellular development and tumorigenesis in lymphoid tissue [1-3]. Most knowledge of the miR-17-92a cluster in normal and abnormal conditions of the lymphoid system is based on mouse experiments. The absence of miR-17-92a up-regulates BIM, which inhibits B-cell development at the pro-B to pre-B transition [4]. High expression of miR-17-92a in transgenic mice leads to expansion of the CD4+ lymphocyte pool, and the na?ve CD4+ cells show recruitment and activation of phosphatidylinositol-3-OH-kinase via suppression of PTEN [3,5]. This suggests that the accumulation of activated CD4+ T cells by higher mir-17-92a expression leads to a breakdown of T-cell tolerance in the periphery and may promote B-cell activation, germinal centre reaction and autoantibody generation.In humans, however, senescence of lymphocytes in vivo occurs through maturation of antigen-stimulation, and thereby subset fractions of lymphocytes gradually change with age; for example, an increase of memory T cells takes place by progressive na?ve T-cell reduction. Although miR-17-92a expression is crucial for lymphocyte development, only limited reports on in vivo human lymphocyte senescence exist. We therefore set out to determine miR-92a levels in peripheral blood lymphocytes obtained from healthy individuals to ascertain the possible association between the expression level of miR-17-92a and ageing.The miR-92a in separated CD8+ T cells decreased significantly with age (P = 0.0002) (Figure 1-A), and miR-92a in CD4+ cells tended to decrease with age (P = 0.0635) (Figure 1-B) (Additional file 1 Table S1). The percentage of RO-CD8+CD27+ (Figure 1-C) and CD3+CD8+CD62L+ fractions (Figure 1-D) also significantly decreased

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