Glycans as Key Checkpoints of T Cell Activity and Function

[Violeta]

November, 2018

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02754/full

Remarkable findings have been highlighting the essential contributions of glycosylation in the regulation of both innate and adaptive immune responses with important implications in the pathogenesis of major diseases such as autoimmunity and cancer

Besides being actively involved in pathogen recognition through interaction with glycan-binding proteins (such as C-type lectins), glycans have been also shown to regulate key pathophysiological steps within T cell biology such as T cell development and thymocyte selection; T cell activity and signaling as well as T cell differentiation and proliferation.

This review discusses how specific glycans (with a focus on N-linked glycans) act as regulators of T cell biology and their implications in disease.

 

[Violeta]

SARS-CoV-2 Infection Drives a Glycan Switch of Peripheral T Cells at Diagnosis​

https://journals.aai.org/jimmunol/a...ARS-CoV-2-Infection-Drives-a-Glycan-Switch-of

In this study, we demonstrated that SARS-CoV-2 infection results in a glycosylation reprogramming of circulating lymphocytes at diagnosis.

We identified a specific glycosignature of T cells, defined upon SARS-CoV-2 infection and apparently triggered by a serological factor.

This specific glycan switch of T cells is detected at diagnosis being more pronounced in asymptomatic patients.

We further demonstrated that asymptomatic patients display an increased expression of a viral-sensing receptor through the upregulation of DC-SIGN in monocytes. We showed that higher levels of DC-SIGN in monocytes at diagnosis correlates with better COVID-19 prognosis.

This new evidence pave the way to the identification of a novel glycan-based response in T cells that may confer protection against SARS-CoV-2 infection in asymptomatic patients, highlighting a novel prognostic biomarker and potential therapeutic target.

 

[LINE]

Well written, thanks for sharing.

Glycans act in the intestinal tract and are involved with a number of factors including the microbiome, I think that Bacteroides thethaiotaumicron is the prominent bacterium that degrades glucans, Research indicates that this bacterium is on the low levels of chronic problems. I think this is why ill people have problems with glycans (polysaccharides).
https://www.sciencedirect.com/science/article/abs/pii/S014181302100828X

There have been significant studies on the microbiome of long covid and it is clear that microbial diversity has shifted. Sabine Hazan MD has posted multiple findings on bifidobacterium being low.

 

[Violeta]

Well written, thanks for sharing.

Glycans act in the intestinal tract and are involved with a number of factors including the microbiome, I think that Bacteroides thethaiotaumicron is the prominent bacterium that degrades glucans, Research indicates that this bacterium is on the low levels of chronic problems. I think this is why ill people have problems with glycans (polysaccharides).
https://www.sciencedirect.com/science/article/abs/pii/S014181302100828X

There have been significant studies on the microbiome of long covid and it is clear that microbial diversity has shifted. Sabine Hazan MD has posted multiple findings on bifidobacterium being low.

You're welcome.

I was led in this direction by your messages in the thread about microbiome, butyrate, and inflammation.

Mariovitali has a twitter account and has been talking about n-linked glycosylation, and the overlap of the two topics is very interesting.

 

[LINE]

I could not find the mariovitali account - for what it is worth, here is my twitter

https://x.com/Patrick33264855

If could post the mario link, that would be appreciated.

I will be updating more findings soon which is quite interesting. The basis of it is that there are 5 layers to the gut environment that coordinate with each other. It is more complex than traditional education offers.

1. Microbiome
2. Mucin layer
3. Tight junction proteins (epithelial)
4. Lamina propria
5. Submucosal

#4 and 5 hold the important immune cells (Paneth, Dendritic and Chief cells) I am experimenting with specific amino acids (e.g. threonine and serine primarily) which help regulate this area according to research papers. The theory is that these will stabilize the immune cells which should help with the tight junction proteins which helps the mucin layer which impacts the microbiome, and this can also work in reverse since there is interconnectivity. A complex study indeed.

Depending on the situation, I believe that the different layers have to be approached. For some minor issues, perhaps Kefir may help restore the ecology of the gut, for others, a more comprehensive approach is necessary. The latter is what is necessary for me.

 

[Violeta]

It's good to have your input on this! I tagged you in mariovitali's thread about glycosylation.

This is the first time I have heard about layers 4 and 5! Surely they need to be dealt with to make any headway. I am looking forward to learning more about that.

Kefir may have helped me in some ways, for example being able to eat more variety, but my eyes were constantly burning and itching so I figured it contains too much histamine for me and stopped eating it.

 

[LINE]

Thanks for your input, it keeps me going.

I noticed that kefir is better than commercial probiotics but noticed that taking them sometimes irritated my gut. I targeted many areas of the gut which includes the probiotics, prebiotics. I also did targets for the IgA system which is integral this would include Vitamins D3, Vitamin A and colostrum. I also targeted the polysaccharides which is part of the mucin/microbiome - there are a number of polysaccharides, most of them caused further irritation*. I did a laundry list of antimicrobials (long, long list) and still the problem is still there.

Beef stock provided the best bang, I found this through looking at protein structures in the gut lining, stock has abundant glycine and proline which are essential for structure. I mixed in turmeric, Ceylon cinnamon, moringa and many others. That is where I made the most progress.

I have been in Monk Mode for the past 2 months and probably combed through 200 journal citations and found the threonine serine connection. I tried serine before with little result so I purchased threonine (one of the few aminos I have not tried, (done quite a few). I purchased threonine last week and have been dosing that at about 1,500 mg per day and did a controlled experiment with it. It does seem to target the gut, I can tell that through the IBS symptoms have slowed. I did notice some detoxification things going on, I found that threonine can help the antioxidant system, so I am guessing that the threonine is pushing toxins out.

So, my current theory is that the dysregulation of the immune cells are disturbing the other layers which is leading to a disturbed microbiome. A balanced and healthy microbiome is the target. We will see how this works out This will be experiment 12,103 (ha ha).

 

[LINE]

This is an interesting article about a polysaccharide called Xyloglucan. It is found in high amounts in tamarind seed. I found a vendor on Walmart that sells it for less than $20 usd, I just received it and trialing it currently.

This is able to protect the tight junction proteins and apparently acts as mucosal protector. It also works by inhibiting bacterial cell adhesion which is similar to cranberry. They think these types of molecules maybe the next antibiotic because they prevent bad bacteria from sticking to the wall of the intestinal or kidney which cause UTIs.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5877534/

Snippet:
We present the results of in vitro studies in models of intestinal and nasal mucosa and conjunctival cells [1,16,17,22] and in vivo models of intestinal inflammation and diarrhoea, demonstrating its barrier properties against bacterial adhesion and invasion and pro-inflammatory compounds, and the results of clinical studies in which the mucosal protectors have demonstrated their protective effect in patients with gastrointestinal disorders (mainly diarrhoea), urinary tract infections, nasal respiratory diseases and dry eye syndrome [15,23,24,25,26,27,28]

 

[LINE]

Diagram of the intestinal areas that might be helpful

https://www.nature.com/articles/s12276-018-0126-x/figures/1

 

[Violeta]

Very interesting article, I didn't know about xyloglucan. I will have to look into that.

I wish I could eat bone broth. I makes my brain hurt, I think because of the glutamate.

This study may not have anything in it that is new to you, but I want to put it here so I know where to find it when I have a bit more energy.

Davide Ret, at the TU Wien, is currently researching glycosylation related bio-markers w/r/t ME/CFS.

Immunological Patient Stratification in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome​

https://www.mdpi.com/2077-0383/13/1/275

This study aimed to elucidate the relationship between immunological characteristics and intestinal barrier function in ME/CFS patients.

Also, other discussed viral triggers of ME/CFS, like influenza virus A, coxsackievirus, and several members of the Herpesviridae family are known to break mucosal tissue barriers and impair epithelial and microbial barrier functions.

 

[Violeta]

I have been in Monk Mode for the past 2 months and probably combed through 200 journal citations and found the threonine serine connection.

I am reading a paper about dolichol, as it is part of the glycosylation process, and thought it was interesting to see the mention of the two specific amino acids that you mentioned.

I am still looking for the reason that asparagine levels are low in pwME/CFS.

This is from this study:
https://pubmed.ncbi.nlm.nih.gov/9878760/