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Non-coding RNA in T cell activation and function
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
2013 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

For a long time research has focused on the protein-coding mRNA, but there is a complex world of non-coding RNAs regulating the human body that we yet know very little about. Non-coding RNAs (ncRNAs) are involved in modulation of different cell processes including proliferation, differentiation and apoptosis. In the current study the role of ncRNAs in T cell activation and function was investigated. T cells are important mediators of immune responses, for example upon viral infections. The T helper cells (TH or CD4+ cells) are involved in orchestrating immune processes like aiding the activation of macrophages and enhancement of B cell function. The TH1 cell subtype is generally pro-inflammatory and IFNγ-secreting. There are regulatory T (Treg) cells that are involved in downregulation of TH1 cells, to decrease or terminate the immune response. It has been shown that upon repeated stimulation TH1 cells can switch into a Treg-like IL10-secreting anti-inflammatory phenotype.

In the IL10-secreting Treg-like cells the microRNA 150 (miR-150) was found upregulated compared to IFNγ-secreting TH1 cells. Thus, miR-150 was believed to be a candidate in key regulation of the switch between the two phenotypes. Predicted target genes of miR-150 were identified using mRNA arrays investigating down-regulated genes in the IL10-secreting Treg-like subpopulation. In this thesis predicted targets of miR-150 were investigated using luciferase assays. Unfortunately no targets were identified.

Upon isolation of IFNγ-secreting TH1 cells and Treg-like IL10-secreting cells, it was found that the ncRNA 886 (nc886) was upregulated in these activated cells, compared to resting TH cells. This indicates that nc886 has an important role in T cell activation. Nc886 has been shown to inhibit PKR activation in other cell types. The effect of nc886 on protein kinase R (PKR) was therefore investigated. PKR shuts down translation upon activation in response to viral double-stranded RNA or cellular stress. We showed that in an activated T cell phenotype nc886 is affecting PKR upon activation by dsRNA from HIV or synthetic origin. The PKR activation pattern is reversed in a resting T cell phenotype.

Place, publisher, year, edition, pages
2013. , 85 p.
Keyword [en]
ncRNA 886, non-coding RNA 886, microRNA 150, miRNA 150, PKR, T cell activation, luciferase assay
National Category
Medical and Health Sciences Biological Sciences
URN: urn:nbn:se:liu:diva-96966ISRN: LiU-IKE-EX-13/05--SEOAI: diva2:644795
Subject / course
Biomedical Laboratory Science
Available from: 2014-10-08 Created: 2013-09-02 Last updated: 2014-10-08Bibliographically approved

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