Onderzoekers van het National Centre for Neuroimmunology and Emerging Diseases hebben
de interne response (MPAK pathways) van
CD56bright en CD56dim NK cellen onderzocht.
Na stimulatie met K562 kankercellen vertoonden de CD56dim NK-cellen van ME/CVS-patiënten een
afname van ERK1/ERK2. De CD56bright NK-cellen lieten een toename van MEK1/MEK2 en p38 zien.
De auteurs relateren de afname van ERK1/ERK2 aan de verminderde werking (cytotoxiciteit) en bren-
gen de toename van MEK1/MEK2 en p38 in verband met inflammatie (verhoogde cytokine-productie):
twee schijnbaar tegengestelde afwijkingen van het afweersysteem die in ME/CVS gevonden worden.
De auteurs stellen dat dit mogelijk veroorzaakt wordt door continue blootsteling aan zieke cellen...
Voor een korte toelichting op deze studie, klik op onderstaande afbeelding:
ERK1/2, MEK1/2 and p38 downstream signalling molecules
impaired in CD56dimCD16+ and CD56brightCD16dim- natural killer cells
in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.
J Transl Med. 2016 Apr 21; 14: 97. doi: 10.1186/s12967-016-0859-z.
Huth TK, Staines D, Marshall-Gradisnik S.
Abstract
Background
Natural Killer (NK) cell effector functions are dependent on
phosphorylation of the mitogen-activated protein kinases (MAPK) pathway
to produce an effective immune response for the clearance of
target cells infected with viruses, bacteria or malignantly transformed cells.
Intracellular signals activating NK cell cytokine production and cytotoxic activity
are propagated through protein phosphorylation of MAPKs including MEK1/2, ERK1/2, p38 and JNK.
Reduced NK cell cytotoxic activity is consistently reported
in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients and
intracellular signalling by MAPK in NK cells remains to be investigated.
Therefore, the purpose of this paper was to investigate
MAPK downstream signalling molecules in NK cell phenotypes from CFS/ME patients.
Methods
Flow cytometric protocols were used to measure
phosphorylation of the MAPK pathway in CD56brightCD16dim/- and CD56dimCD16+ NK cells
following stimulation with K562 tumour cells or phorbol-12-myristate-13-acetate plus ionomycin.
NK cell cytotoxic activity, degranulation, lytic proteins and cytokine production were also measured
as markers for CD56brightCD16dim/- and CD56dimCD16+ NK cell function
using flow cytometric protocols.
Results
CFS/ME patients (n = 14) had a significant decrease in ERK1/2 in CD56dimCD16+ NK cells
compared to the non-fatigued controls (n = 11) after incubation with K562 cells.
CD56brightCD16dim/- NK cells from CFS/ME patients
had a significant increase in MEK1/2 and p38 following incubation with K562 cells.
Conclusions
This is the first study to report
significant differences in MAPK intracellular signalling molecules
in CD56dimCD16+ and CD56brightCD16dim/- NK cells from CFS/ME patients.
The current results highlight the importance of
intracellular signalling through the MAPK pathway for
synergistic effector function of CD56dimCD16+ and CD56brightCD16dim/- NK cells
to ensure efficient clearance of target cells.
In CFS/ME patients,
dysfunctional MAPK signalling may contribute to reduced NK cell cytotoxic activity.
Keywords:
Natural killer, Cytotoxic, Cytokine, Intracellular signalling,
Mitogen-activated protein kinase signalling, Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
http://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-0859-z
Met dank aan Manja ("onbetaalde news watcher").
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