Aged T cell subsets are characterized by a distinct microRNA signature
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1
University Medical Center Groningen, University of Groningen, Department of Pathology and Medical Biology, Netherlands
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2
University Medical Center Groningen, University of Groningen, Department of Rheumatology and Clinical Immunology, Netherlands
Objective
Decline of immunological responsiveness in elderly correlates with changes in the composition of the T cell compartment. Recently, microRNAs (miRNA) have emerged as important players in the regulation of T cell development, differentiation and function. However, comprehensive insight into the contribution of miRNAs to T cell age-related changes remains elusive. The aim of this study was to investigate the age associated changes in miRNA expression within defined T cell subsets in young and old healthy individuals.
Materials and Methods
T cell subsets (naïve, memory, CD4 and CD8 cells) derived from young and elderly healthy subjects were sorted based on CD3, CD4, CD45RO and CCR7 expression. MiRNA expression patterns were determined using the agilent human miRNA microarray platform (V2) based on Sanger miRbase (release 10.1). Results were validated by miRNA-specific qRT-PCR.
Results
Hierarchical clustering showed differential expression of miRNAs mainly between naive and memory T-cell subsets. Age related differential expression was observed predominantly within the naive CD45RO- T-cell population. 17 miRNAs showed at least 2 fold up- or downregulation in aged naïve T cells. Analysis of individual samples revealed a statistically significant age related upregulation for miR-21, miR-223 and miR-451 by qRT-PCR. Moreover, age-related upregulation of miR-21 was associated with age-dependent accumulation of end-stage differentiated CD8 T cells.
Conclusion
Age-related changes in miRNA expression are found predominantly within the CD45RO- T cell compartment that converges with the accumulation of end-stage differentiated CD45RO- T cells.
Keywords:
T cells,
Ageing,
microRNA,
microRNA array,
microRNA expression changes
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Teteloshvili
N,
Van Den Berg
A,
Van Der Geest
N,
Van Der Lei
R,
Jellema
P,
Brouwer
E,
Boots
AH and
Kroesen
B
(2013). Aged T cell subsets are characterized by a distinct microRNA signature.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00994
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Received:
28 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Mrs. Nato Teteloshvili, University Medical Center Groningen, University of Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands, n.teteloshvili@umcg.nl