In the gut, immunity is a two-way street: dysbiosis and T cells

natasa778

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http://www.sciencedaily.com/releases/2014/07/140710130613.htm

great --- now only the million dollar question remains, how to reconstitute faulty immune cells? (and I mean safely, easilly and without breaking the bank ;)


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In the study, the group demonstrated that the regulation by immune T cells of immunoglobulin A (IgA), an antibody that plays a key role in immunity in the gut, is critical for the maintenance of rich bacterial communities in mammal guts.


They began by studying mice with various immune deficiencies and attempted to restore the mice by providing the missing components. They monitored the bacterial communities in the mice's guts with or without the reconstitutions and evaluated the flow of information between the immune system and bacteria. They discovered that the precise control of IgA production by regulatory T cells is critical for keeping a rich and balanced bacterial community.

To investigate how bacteria feed back to the host, they looked at germ-free mice (mice born and maintained sterile in special incubators) and young pups that had been transplanted with different bacterial communities (either by injection of bacteria or by painting the fur with fecal bacteria extracts from normal or immune-deficient mice). They discovered that the immune system "sees" and responds differently to different bacterial communities. Rich and balanced bacterial communities seem to be perceived as "self" and induce a quick maturation of the immune system and gut responses (induction of regulatory T cells and IgA), while a poor and unbalanced bacterial community is apparently perceived as "non-self" and induces responses aimed at eliminating it (T cells with inflammatory properties and IgG or IgE responses).

According to Sidonia Fagarasan, who led the work, "This study should have an impact on the way we understand immune-related disorders associated with bacteria dysbiosis in the gut. In order to reestablish a healthy state we need to interfere not only with the bacteria, by providing probiotics or through fecal transplantation, but also with the immune system, by correcting the faults caused either by inherited deficiencies or by aging."

"It was surprising," she continues, "to see how the reconstitution of T cell-deficient mice with a special regulatory T cell type leads to dramatic changes in gut bacterial communities. It was spectacular to see how the immune system perceives and reacts to different bacteria communities. It gives us hopes that with a better knowledge of the symbiotic relationships between the immune system and bacteria in the gut, we could intervene and induce modifications aiming to reestablish balance and restore health."
 

melihtas

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This study might explain why most of us have gut problems before we got ME. I think we are not even close to finding a cure for ME since we don't even know how it started and what caused it.

Schematic representation from the original source: http://www.riken.jp/en/pr/press/2014/20140711_1/

figure1-en-pr.jpg

Cecal bacteria from mice with rich (left panel) or poor (right panel) bacterial communities

figure2-en-pr.jpg

Schematic representation of the regulatory loop between host immune system and gut bacteria
 

melihtas

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Dietary Folic Acid Promotes Survival of Foxp3+ Regulatory T Cells in the Colon

Abstract
Dietary compounds as well as commensal microbiota contribute to the generation of a unique gut environment. In this study, we report that dietary folic acid (FA) is required for the maintenance of Foxp3+ regulatory T cells (Tregs) in the colon. Deficiency of FA in the diet resulted in marked reduction of Foxp3+ Tregs selectively in the colon. Blockade of folate receptor 4 and treatment with methotrexate, which inhibits folate metabolic pathways, decreased colonic Foxp3+ Tregs. Compared with splenic Tregs, colonic Tregs were more activated to proliferate vigorously and were highly sensitive to apoptosis. In colonic Tregs derived from mice fed with a FA-deficient diet, expression of anti-apoptotic molecules Bcl-2 and Bcl-xL was severely decreased. A general reduction of peripheral Tregs was induced by a neutralizing Ab against IL-2, but a further decrease by additional FA deficiency was observed exclusively in the colon. Mice fed with an FA-deficient diet exhibited higher susceptibility to intestinal inflammation. These findings reveal the previously unappreciated role of dietary FA in promotion of survival of Foxp3+ Tregs that are in a highly activated state in the colon.

Knowing that people with ME have folic acid problems and some of us get better on methylation protocol or high dose methylfolate. Can this be the reason for Treg anomalies?

We also have very low Vitamin D levels.

Vitamin D Status Is Positively Correlated with Regulatory T Cell Function in Patients with Multiple Sclerosis

In several autoimmune diseases, including multiple sclerosis (MS), a compromised regulatory T cell (Treg) function is believed to be critically involved in the disease process. In vitro, the biologically active metabolite of vitamin D has been shown to promote Treg development. A poor vitamin D status has been linked with MS incidence and MS disease activity. In the present study, we assess a potential in vivo correlation between vitamin D status and Treg function in relapsing remitting MS (RRMS) patients.
 
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melihtas

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Istanbul Turkey
A Pivotal Role of Vitamin B9 in the Maintenance of Regulatory T Cells In Vitro and In Vivo

Dietary factors regulate immunological function, but the underlying mechanisms remain elusive. Here we show that vitamin B9 is a survival factor for regulatory T (Treg) cells expressing high levels of vitamin B9 receptor (folate receptor 4). In vitamin B9-reduced condition in vitro, Treg cells could be differentiated from naïve T cells but failed to survive. The impaired survival of Treg cells was associated with decreased expression of anti-apoptotic Bcl2 and independent of IL-2.In vivo depletion of dietary vitamin B9 resulted in the reduction of Treg cells in the small intestine, a site for the absorption of dietary vitamin B9. These findings provide a new link between diet and the immune system, which could maintain the immunological homeostasis in the intestine.
 

Bob

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Anyone interested in the above, might be interested in the following article...

Culturing For Cures
UCSF Scientists Explore the Bacterial Communities that Live In and On Our Bodies to Find Treatments for Disease
By Claire Conway
June 03, 2014
http://www.ucsf.edu/news/2014/05/114656/culturing-cures

It's a long and varied article, so I can't summarise it.
But here's a tiny extract that gives a flavour:
The chemical produced by B. fragilis [a gut bacterium] interacts with a type of human immune cell called a natural killer T cell. That meant it could be very useful in treating allergic and autoimmune diseases.
 
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Sasha

Fine, thank you
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UK
Anyone interested in the above, might be interested in the following article...

Culturing For Cures
UCSF Scientists Explore the Bacterial Communities that Live In and On Our Bodies to Find Treatments for Disease
By Claire Conway
June 03, 2014
http://www.ucsf.edu/news/2014/05/114656/culturing-cures

It's a long and varied article, so I can't summarise it.
But here's a tiny extract that gives a flavour:

There's an amazing story at the start of that article about a guy who cures his own ear infection in a novel way - worth the read just for that!
 

Sasha

Fine, thank you
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UK
Thanks, @Bob - that's one of the most interesting articles on the microbiome in relation to health that I've read (and a very easy read for a layperson, too).
 
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