Calcium Lets T Cells Use Sugar to Multiply & Fight Infection

thegodofpleasure

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I came across this thanks to Dr Derya Unutmaz tweeting about work done by his friend and collaborator, Dr Stefan Feske.

http://nyulangone.org/press-releases/calcium-lets-t-cells-use-sugar-to-multiply-fight-infection

A calcium signal controls whether immune cells can use the nutrients needed to fuel their multiplication into a cellular army designed to fight invading viruses. This is the finding of a study in human cells and mice led by researchers at NYU School of Medicine and published online October 10 in Immunity.

The study results concern the precise and massive immune counterattack by T cells in response to viral infection. When this type of white blood cell is turned on by an invader, it divides and multiples into an army of clones primed specifically to attack that invader.

The current study found that whether or not T cells can use energy from blood sugar, or glucose, to multiply depends on calcium flow into cells, a mechanism not previously recognized, say the authors.

Upon receiving the right signal—which in this case is the recognition of virus particles—T cells open channels in their outer membranes, letting calcium rush in to activate the protein NFAT, a transcription factor that turns on genes, say the researchers. Specifically, the new study shows that a particular type of calcium influx—store-operated calcium entry (SOCE)—controls the activation of NFAT and its ability to turn on genes that control the uptake and breakdown of glucose.

“Our results argue that SOCE, in cooperation with the enzyme calcineurin, regulates the conversion of glucose into cellular energy and building blocks needed for T cell proliferation,” says senior author Stefan Feske, MD, an associate professor in the Department of Pathology’s Experimental Pathology Research Laboratory at NYU School of Medicine.

How relevant is this discovery to the work done by Don Staines & Sonya Marshall-Gradisnik, which showed impaired Calcium signalling in the T & B cells of ME/cfs patients ?
 

Wonko

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So I should get with the program and chow down on some bones right now? Milk? Cheese? Calcium, magnesium, zinc, copper, fish oil capsules?

Oddly, when I was on them, calcium channel blockers helped quite a but, with pain, which made me feel better and allowed me to be a smidge more active. Which appears to be the opposite of this.
 

Wonkmonk

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But when immune overactivation, including T-cells, is part of the problem - as it may be for some patients - then more calcium is counterproductive.

In my case, calcium and Vitamin D in high dose massively worsened my symptoms and it got better after I stopped taking them. I read the same from several others in the Forum.

That would also be a possible explanation why calcium blockers help (assuming they also block T-Cells).

Hmm...so much speculation, so little knowledge :rolleyes:
 

GreyOwl

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I don’t think this research relates to dietary recommendations @Wonkmonk. It’s describing research into a previously unknown mechanism in a metabolic/immune pathway.
 

Wonkmonk

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Thank you for your explanation, Prof. Edwards.

If I may ask, what could be the reason why high Vitamin D supplements make some patients worse?

I have seen at least a dozen such reports here in the forum and in my case. And it happened three times over 2 years, each time I pushed Vitamin D over 35 ng/ml (which is in the middle of the range of my lab), I got considerably worse, and then better as I stopped taking VD.
 
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If I may ask, what could be the reason why high Vitamin D supplements make some patients worse?
I have no particular idea about that. But it does not surprise. The hypothalamus has a very sophisticated way of telling us what it wants and what it has had enough of. If you eat lots of fish you may well feel you would rather have some pasta. If you eat lots of chocolate you are likely to feel awful. I would to be surprised if eating more vitamin D than you need triggers the hypothalamus to say 'not more of those pills, for goodness sake'.
 
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This could be relevant to patients given that Mark Davis (Stanford immunology hot shot) has found proliferation of T cells in CFS*, a similar pattern to that scene in cancer, infections and Multiple Sclerosis - but not in healthy controls.

Proliferation of T cells usually means activation in response to a threat, hence the title "calcium let's T cells use sugar to proliferate and fight virus infections". Though Jonathan Edwards has cautioned that when others have looked at CFS they haven't found evidence for activation of T cells and something more complex might be going on.

Davis's work hasn't been published yet, but if it pans out and is replicated it's possible (And I'm just speculating here) that it could be treated using drugs that dampen down proliferation, such as the two mentioned in this piece.

Just to explain a bit more about the research:

The authors discovered a previously-unknown mechanism for controlling T cell proliferation, calcium flowing into cells and switching on the genes leading to production the enzymes needed to make use of blood sugar. This is needed to fuel fuels their replication and division, leading to a small army of clones.

When calcium enters the cell it activates an enzyme called Calcineurin that in turn activates the transcription factor, causing it to move into into the cell nucleus. Here it binds to DNA and acts as a master switch, turning on a set of genes that control production of the proteins the cell needs to make use of glucose and so power cell division and growth.:

Calcium >> gene activation >> glucose uptake and metabolising proteins >> energy tor proliferation

Cyclosporine A and tacrolimus, the two immune-suppressing drugs mentioned, block calcineurin from activatinng the transcription factor and so stops the cells from been able to access the energy they need to proliferate.


* dictated using phone voice recognistion, and you try getting it to recognise "mecfs"...
 

Aroa

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Dr Derya Unutmaz is also tweeting this . Would this mean that T-cell clonal expansion is not due to an autoimmune process ?

Derya Unutmaz chart.jpg