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Hi Jonathan, I completely agree, that we can't presume purely myeloid compartment playing a role. This simply doesn't exist in the body. Everything is interconnected. What is really needed now is systemic analysis of immune system. I think what I've seen so far that this analysis is warranted...

I apologize, I misunderstood. How do you envision a role of adaptive immune system in the disease? Do you expect autoimmunity targeting neurons (cytotoxic T cells or autoantibodies)? If I'm not wrong that doesn't seem to be the case. Or something more like dysfunctional Treg cells leading to...

Yes, Irg1 is expressed in monocytes, macrophages, neutrophils and to some extent in dendritic cells. My assumption is that the effect of itaconate we observe in macrophages will also work in monocytes. I don't doubt that Prdx5 and SDH will be inhibited by itaconate. If it will translate into...

We did Irg1 knock-out. This is different from knock-down. In case of knock-down, you are decreasing protein expression by targeting mRNA. Usually efficiency around 50-90% decrease. In the case of knock-out, you delete the gene encoding your protein in the animal. Resulting in a complete loss of...

You don't want to use SDH inhibitors as therapeutics. They can be helpful in some cases. But one of the side effects is Alzheimers.

This all is ongoing and experiments are running. I have reason to believe (I have experimental proof that is not yet perfect) Prdx3 is not affected. This opens huge avenue of novel research on multiple fronts. It remains to be seen, whether it is also in ME/CFS. I hope it does. But we need a...

Please allow me to adjust some of the points. 1. You are absolutely correct. The problem arises especially when people use derivatives of itaconate and simply call it itaconate. 2. 2-Methyl succinct acid is not Irg1 inhibitor. Just like itaconate, it inhibits PRDX5, boosts IFNb production and...

@Jonathan Edwards @jnmaciuch Itaconate uptake has been shown for number of cell types, including T cells. But, one thing has to be considered and this is where I'm not yes convinced these effects can be driven by itaconate transfer to other cells. Itaconate is not a very potent inhibitor of...

One type of glial cells are microglia. These are essentially brain macrophages. They are innate immune cells that can get activated by myriad of signals and are known to produce itaconate. As we show in the paper the signal can be Damage associated patterns or Pathogen associated patterns. They...

Hi Jonathan, This is indeed very deep and requires some thought. I agree that cellular basis of ME/CFS is very much needed to be understood. Obvious go to would be neurons. I would expect changes there. But those are likely consequences of some other change. The hypothesis of Rob and Ron...

Max Artyomov (priciple investigator in this story) has a talk in Harvard seminar series. It just came to my attention that it will be streamed on zoom tomorrow. It will be scientifically heavy talk. But some of you may find it interesting...

Thank you! This will help for sure.

Thank you, I'll do my best to get to this. Currently working on many fronts. plus i'm getting ready to speak to leaders in ME/CFS research. Sorry for not reacting readily.

Here is a little backstory of our discovery. It is public and short. Should be accessible to everyone. https://communities.springernature.com/posts/itaconate-and-prdx5-how-did-we-get-here

I like this idea. Since ME/CFS is mostly self reported (correct me if I'm wrong, please) this would be a key step in understanding and categorizing people in a study. We can talk about this in a more detail.

Thank you! Let me know if there is more I can explain.

I understand, you make a good point here. But, what can be done is to record the meeting and people can come back to it and listen to it in bite sized portions on their own pace if interested. I don't have any proffesional recording equipment, so I wouldn't be able to do production to be...

If you'd like, I can organize a mass zoom meeting, where I will explain our findings in more detail so that everyone can understand. Would you be interested? We can start a thread to fing out if people like the idea.

Sorry for that. Open access is crazy expensive. My paper is also available on researchgate with the fulltext. https://www.researchgate.net/publication/390924021_Itaconate_modulates_immune_responses_via_inhibition_of_peroxiredoxin_5 Let me know if it works for you.

Hi tuha, This is wonderful. Can you share who's the long covid group? We are planning things on the fly at the moment. But this could be an amazing resource in the near future if people would be willing to participate in a study. 1000 people is a great number.