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Derya Unutmaz t-cell findings and gut connection

Murph

:)
Messages
1,799
Cort has written this excellent piece, including some huge tidbits on t-cell research from Unutmaz.


https://www.healthrising.org/blog/2017/12/09/me-cfs-researcher-patients-shine-nih-call/ it is way more interesting than the title suggests....

The next five paragraphs are excerpts of Cort's blog post.

in response to a great question during the Q&A period, Unutmaz revealed that the most provocative findings found were in the T-cells, and that the findings have proved to be highly reproducible – something we’ve rarely seen outside of NK cells (cousins, it should be pointed out, to T-cells) – in the immune field in ME/CFS.

the T-cell abnormalities Unutmaz is finding are associated with the gut probably made Mady Hornig and Ian Lipkin – champions of the role that the gut may play in ME/CFS – smile. It turns out that the problematic T-cells Unutmaz is finding regulate gut functioning. Either something in the guts of ME/CFS patients is messing with the regulatory T-cells or the gut T-cells are simply sitting down on their job. Either way, Unutmaz’ findings appear to put an enhanced focus on the gut in ME/CFS.

he gut is a terribly complex place, but with more and more research focusing on it and new methods being developed to understand it, a central problem in the gut might not be a bad thing at all to find in ME/CFS. Unutmaz echoed that hope when he stated that much is known about the cells he’s finding problems in and many treatments are under development to deal with them. That’s very good news for a disease that’s seemed particularly good at featuring issues with cells about which not much is known.

Unutmaz said he’ll be following up his T-cell study with a deep and rigorous probe of the gut bacteria in ME/CFS. He won’t just determine which bacteria are there – he’ll actually stress ME/CFS patients to see how their gut bacteria react. His studies will generate a lot of data; the challenge with them, as with all “omics” studies, will be to separate the wheat from the chaff.

Unutmaz is also working with Precisely to develop an app to collect clinical data worldwide on ME/CFS patients. We’ve heard of projects like this before, but this may be the first one that has the funding to come to fruition.
 
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dreampop

Senior Member
Messages
296
Finally info on the Unutmaz finding. My first question is, is it a function of SIBO/decreased diversity etc? In which case it might not be as promising. My second question would be, is it involved in the pathology? Obviously unanswerable at the moment.

I have been hesitant of ME/CFS models that center on the gut, but this might be a new thing altogether.

The final question I guess, is what kind of T-Cells, since some research shows quite a few kinds of t-cells have gut-specific versions. We know they regulate gut functioning, but that could probably be said about most of them in some way or another. @Cort maybe has more details?
 

me/cfs 27931

Guest
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1,294
Having a sibling who died of T-Cell (non-Hodgkin) lymphoma at age 26, I’ve long suspected aberrant T-cells might play a role in my ME/CFS.
 

Gemini

Senior Member
Messages
1,176
Location
East Coast USA
interesting... I wonder how T-cells and gut bacteria interact
@Jesse2233 a recent discovery in cancer immunotherapy research ties specific gut bacteria[species] to T-cell functioning ultimately impacting cancer drug effectiveness in patients.

In a specific case the A.muciniphila species associated with the gut's mucus lining causes the cytokine IL12 to be released which primes T-cells and improves patient's response to PD-1 blocker drugs.

http://forums.phoenixrising.me/inde...munotherapy-drug-response-thru-t-cells.56571/

The level of detail in this research down to bacteria species is impressive. Maybe the efforts of Unutmaz, Mark Davis, Lipkin and others studying the microbiome and/or T-cells in ME/CFS will be too and similarly lead to treatments.
 
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ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
interesting... I wonder how T-cells and gut bacteria interact

This might be helpful-

Relationship between gut microbiota and development of T cell associated disease

Abstract
The interplay between the immune response and the gut microbiota is complex. Although it is well-established that the gut microbiota is essential for the proper development of the immune system, recent evidence indicates that the cells of the immune system also influence the composition of the gut microbiota.

This interaction can have important consequences for the development of inflammatory diseases, including autoimmune diseases and allergy, and the specific mechanisms by which the gut commensals drive the development of different types of immune responses are beginning to be understood.

Furthermore, sex hormones are now thought to play a novel role in this complex relationship, and collaborate with both the gut microbiota and immune system to influence the development of autoimmune disease. In this review, we will focus on recent studies that have transformed our understanding of the importance of the gut microbiota in inflammatory responses.

Interestingly, the intestinal microbiota affects the immune and/or inflammatory status of the host by modulating intestinal barrier function and by influencing the development of the immune response.

Several gut microbial structures that play an important role in barrier functions have been identified. The secreted protein, p40, from Lactobacilli LGG ameliorates cytokine-mediated apoptosis and disruption of the gut epithelial barrier [1], and flagellin from Escherichia coli Nissle is associated with induction of β-defensin 2 in epithelial cells [2].

Gut microbiota
has been shown to direct maturation of the host immune system [3], to play a key role in the induction of immunoglobulin (Ig) A [4,5] and germinal centers [6], and to drive Th1, Th17, and regulatory T cell (Treg) development in the gut [7–9].

Full paper here.

Jim
 

Forbin

Senior Member
Messages
966
Unutmaz said he’ll be following up his T-cell study with a deep and rigorous probe of the gut bacteria in ME/CFS.

I hope he looks at other microbes of the gut in addition to bacteria, like fungi.
 
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dreampop

Senior Member
Messages
296
From the full transcript,

"... specific subsets that were so perturbed go to our mucosa, especially to the gut mucosa, and they’re there to check on, you know, the trillions of bacteria on the other side of the border... And if, you know, we don’t know why this is happening, whether it’s the destruction of the microbiome causing it or the immune system is destructed and that’s causing the changes to the microbiome and that’s actually something that we’re looking at."

This is the part that is dampening my excitement because it might just be something that happens when the gut is messed up, as the study already posted in this thread shows. My worry is that the 'perturbations' can go either way, too high or too low, suggesting that is gut-driving the immune system finding. So my worry is the 'big' finding might not even be CFS specific. It would be big if it is, but even then it might not directly be pathological, and that's a lot of money on the gut.
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
Abstract
In the mucosa, the immune system's T cells and B cells have position-specific phenotypes and functions that are influenced by the microbiota. These cells play pivotal parts in the maintenance of immune homeostasis by suppressing responses to harmless antigens and by enforcing the integrity of the barrier functions of the gut mucosa.

Imbalances in the gut microbiota, known as dysbiosis, can trigger several immune disorders through the activity of T cells that are both near to and distant from the site of their induction.

Elucidation of the mechanisms that distinguish between homeostatic and pathogenic microbiota–host interactions could identify therapeutic targets for preventing or modulating inflammatory diseases and for boosting the efficacy of cancer immunotherapy.
https://www.ncbi.nlm.nih.gov/pubmed/27383982/