De groep van Brenu, Staines en Peterson en kollega's,
die recent een studie over verlaagde cytotoxiciteit van NK-cellen in ME/CVS publiceerden,
hebben tevens de genexpressie van microRNAs van NK- en CD8+ T-cellen onderzocht.
MicroRNAs (miRNAs) zijn kleine moleculen die de expressie van diverse genen beïnvloeden
(door een eiwitproductie of genexpressie-stap af te remmen:
translationele repressie, of
door messenger RNA, tussenproducten van die eiwitproductie, te verknippen: cleavage).
De verlaagde genexpressie van miRNA in NK cellen, remt de werking van die NK cellen af.
Enkele relevante citaten uit deze studie:
Dysregulation in the expression of miRNAs may adversely affect immune homeostasis.
MicroRNAs are also essential for modulating immune responses to bacterial and viral infection.
...
Although the action of these miRNAs in cytotoxic cells is not explicitly known,
the genes targeted by these miRNAs .. may suggest an involvement in the cytotoxic activity of NK cells.
Hence a decrease in their expression may reduce the induction of cell death and
potentially affect the commitment of these cells to trigger apoptosis of viral infected cells in CFS/ ME.
...
Although, the current literature on the influences of these miRNAs on NK and CD8+T cell related lytic proteins, receptors and cytotoxic activity is limited,
the presence of similar expression levels of miRNAs in both cells suggests a common pathway of the miRNAs in these cells.
Cytotoxic lymphocyte microRNAs as prospective biomarkers
for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.
Brenu EW, Ashton KJ, van Driel M, Staines DR,
Peterson D, Atkinson GM, Marshall-Gradisnik SM.
J Affect Disord. 2012 May 7. doi:10.1016/j.jad.2012.03.037.
Background:
Immune dysfunction associated with a disease often has a molecular basis.
A novel group of molecules known as microRNAs (miRNAs)
have been associated with
suppression of translational processes involved in
cellular development and proliferation, protein secretion,
apoptosis, immune function and inflammatory processes.
MicroRNAs
may be implicated in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME),
where immune function is impaired.
The objective of this study was to determine
the association between miRNAs in cytotoxic cells and CFS/ME.
Methods:
Natural Killer (NK) and CD8+T cells
were preferentially isolated from peripheral blood mononuclear cells
from all participants
(CFS/ME, n=28; mean age=41.8±9.6 years and
controls, n=28; mean age=45.3±11.7 years),
via negative cell enrichment.
Following total RNA extraction and subsequent synthesis of cDNA,
reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used
to determine the expression levels of nineteen miRNAs.
Results:
There was a significant reduction in the expression levels of miR-21,
in both the NK and CD8+T cells in the CFS/ME sufferers.
Additionally,
the expression of
miR-17-5p, miR-10a, miR-103, miR-152, miR-146a, miR-106, miR-223 and miR-191
was significantly decreased in NK cells
of CFS/ME patients in comparison to the non-fatigued controls.
Limitations:
The results from these investigations are not yet transferable into the clinical setting,
further validatory studies are now required.
Conclusions:
Collectively these miRNAs have been associated with
apoptosis, cell cycle, development and immune function.
Changes in miRNAs in cytotoxic cells
may reduce the functional capacity of these cells and
disrupt effective cytotoxic activity
along with other immune functions in CFS/ME patients.
Keywords:
MicroRNAs, Cytotoxic, Natural Killer cells, Chronic fatigue
PMID: 22572093
http://www.sciencedirect.com/science/article/pii/S0165032712002376
Met dank aan Manja en Rob.
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