Adrian Liston Profile picture
May 26, 2022 12 tweets 25 min read Read on X
Excited to share our new paper out at @NatImmunol today! We discovered the limiting factor for #brain #Tregs is #IL2, and developed a new #genetherapy to treat #traumaticbraininjury and other #neuroinflammatory pathologies. 1/12

nature.com/articles/s4159…
The work started more than 10 years ago, after my brother Russell died following a #traumaticbraininjury. The more I read into it, the more treatable #neuroinflammation seems. Obviously there is a #brain delivery problem, but stopping #inflammation is basic #immunology! 2/12 Image
We had a great post-doc, @EmanuelaPasciu1, drive a project showing #Tcells in mouse and human brain, with key functions. Among these T cells were a small population of anti-inflammatory #Tregs, again in mouse and human. 3/12
cell.com/cell/fulltext/…
@EmanuelaPasciu1 So we knew there were #Tregs in the #brain, even under healthy conditions, but the numbers don't seem high enough to control #inflammation and promote repair after injury. The mission was clear: find and deliver the limiting factor in #traumaticbraininjury! Enter @ys_lidia. 4/12 Image
@EmanuelaPasciu1 @ys_lidia Key experiments with @jldvib demonstrated that the limiting factor for #brain #Tregs was the low survival rate in the brain. Work in the lab from @wullfbyte, going back more than a decade, demonstrated that #IL2 controls the survival rate of Tregs. 5/12
nature.com/articles/ni.26…
We teamed up with Matthew Holt @CBD_VIB @i3S_UPorto to design a system to feed extra #IL2 into the brain. The gene delivery system harnesses #genetherapy technology and #astrocyte biology, to bring brain IL2 levels up to the same level as the blood. 6/12
The system increases #brain #Tregs 10-fold, creating an anti-inflammatory environment. With @PascalBielefeld @FitzFitzsimons @UvA_Amsterdam we tested in #traumaticbraininjury, and the results were immediate - we were able to prevent most neurological damage! 7/12 Image
@PascalBielefeld @FitzFitzsimons @UvA_Amsterdam @sebastianmunck @BioImagingCore The great thing about this approach is that #Tregs are smart anti-inflammatory agents, able to deal with many different types of stress. We could hit with models of #stroke or #multiplesclerosis and saw the same protective effect! 8/12 Image
@PascalBielefeld @FitzFitzsimons @UvA_Amsterdam @sebastianmunck @BioImagingCore (In fact, our #IL2 treatment even works to prevent cognitive decline or #dementia in normal ageing when given to two year-old mice, but keep that under your hat as it is not yet peer-reviewed. 9/12)
biorxiv.org/content/10.110…
@PascalBielefeld @FitzFitzsimons @UvA_Amsterdam @sebastianmunck @BioImagingCore What next? We'd love to move into a #clinicaltrial. All the pieces are in place (thanks @ERC_Research PoC!) and the tech can be directly translated. Each year 50 million #traumaticbraininjury patients need treatment, and families need hope. 10/12
@PascalBielefeld @FitzFitzsimons @UvA_Amsterdam @sebastianmunck @BioImagingCore @ERC_Research @EmanuelaPasciu1 @ys_lidia @jldvib @BabrahamInst @KU_Leuven @VIBLifeSciences @Vdb_lab @DeStrooperLab @LuVaDeBo @VE_ZSU @StijnVerschore1 Finally, the work couldn't have happened without @ERC_Research, @alzassociation and @BBSRC support. @equinoxgraphics made the videos and the great editorial team at @NatImmunol brought it across the finishing line. My thanks to every one, this will change lives. 12/12

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More from @LabListon

Jun 19
Biggest paper yet from the lab out now in @ImmunityCP! It is a massive #openscience resource on #tissueTregs, and what makes #Tregs tick in the #tissues. Spoiler-alert: Tissue Tregs are really different from what we all thought. 🧵 1/21

sciencedirect.com/science/articl…
Where do #TissueTregs come from? The previous standard model is the "seeding and specialisation" model, where #Tregs enter from tissues, turn on a dedicated transcriptional program per #tissue, and dwell indefinitely in that tissue as specialised cells. 2/21
We had examples of #fatTregs and #muscleTregs becoming unique permanent residents, and the
@ERC_Research funded us to undertake an overly ambitious project to look at everything, everywhere, all at once. Only possible because of the #dreamteam of @jldvib and @olivertburton. 3/21
Image
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Read 21 tweets
Aug 20, 2023
Biggest paper yet from the lab now a #preprint on @biorxivpreprint. A massive #openscience resource on #tissueTregs, and what makes #Tregs tick in the #tissues.

Spoiler-alert: Tissue Tregs are really different from what we all thought. 🧵 1/21

biorxiv.org/content/10.110…
Go back to that sweet innocent time in the spring of 2016. #Brexit was an unlikely joke, @HillaryClinton was cruising to a landslide against some reality TV starlet, and we thought that #TissueTregs formed by seeding tissues and differentiating into unique terminal cells. 2/21 Image
We had examples of #fatTregs and #muscleTregs becoming unique permanent residents, and the @ERC_Research funded us to undertake an overly ambitious project to look at everything, everywhere, all at once.

Only possible because of the #dreamteam of @jldvib and @olivertburton. 3/21
Image
Image
Read 21 tweets
Nov 14, 2022
For anyone doing #flowcytometry, would you like to have a new protocol that reduces your #antibody costs by ~10-fold and also gives you higher quality data, with better signal-to-noise ratio?

Yes? Then read work by @olivertburton and @CarlyEWhyte. 1/6

…rentprotocols.onlinelibrary.wiley.com/doi/epdf/10.10… Image
Bottom-line-up-front: stain overnight. Antibody staining is sensitive to both dilution and time, so a titration that gives crummy staining in 30' can actually give beautiful staining overnight. The best part is, that lower dilution gives less background, for better separation 2/6 Image
You can see this quite clearly with even tricky staining, like #Foxp3 and #cytokines. The overnight stain gives a stronger positive signal without increasing the background at all. Plus your cells are ready in the morning, when the cytometer is free, rather than 8pm at night! 3/6 Image
Read 6 tweets
Jun 8, 2021
We have an exciting new #preprint on @medrxivpreprint ! A novel class of #primaryimmunodeficiency, with the discovery of ITPR3 mutations in two families with combined immunodeficiency. As always, studying #PID teaches us so much about biology! 1/8

medrxiv.org/content/10.110…
The work is based on patients identified @UZLeuven by Rik Schrijvers and @IsabelleMeyts. Both patients had a combined #immunodeficiency with sensitivity to infections, one complicated by peripheral #neuropathy and one by #autoimmune hemolytic anemia. Over to the gene hunters! 2/8
Mutations in ITPR3 were identified by Erika Van Nieuwenhove and Frederik Staels. ITPR3 is part of a #Calcium channel, so we turned to the Serysheva lab @Irina52948708 to predict the impact on structure. Clear as day, the mutations change the charge of the channel. 3/8
Read 8 tweets
Jul 1, 2020
I am really thrilled to release #AutoSpill onto @biorxivpreprint. It is a novel method for applying compensation to #flowcytometry data, which reduces the error by ~100,000-fold. It is thanks to AutoSpill that we can push machines to their max colours

biorxiv.org/content/10.110…
#AutoSpill is a beautiful example of what #maths can add to #immunology, led by the talented Dr Carlos Roca.

It has really open up my eyes to the potential of #computationalbiology, and is the reason why we have a new #datascience position available:

babrahaminstitute.livevacancies.co.uk/#/job/details/…
So how does #AutoSpill work? If you just want to compensate your data, simply upload your single colour controls to autospill.vib.be and then copy the spillover matrix to your #flowcytometry program of choice

@CarlyEWhyte can walk you through the whole process in <2'
Read 20 tweets
May 4, 2020
@sakisci @BetterAcademia @AcademicChatter @OpenAcademics I'm a first gen high-school graduate, now first gen PhD and professor :)

Don't be too scared off by the comments you have here. Most only really apply to the US. I'm assuming that you are doing a biomed PhD in the UK based on your profile, so a few tips... 1/n
@sakisci @BetterAcademia @AcademicChatter @OpenAcademics First, getting into a PhD program is tough. You've made it, congratulations! By definition you have the intellectual ability to finish. Never doubt that.

That said, you will doubt it. Especially at the 3-6 month period and at ~2 years in. That is normal.

2/n
@sakisci @BetterAcademia @AcademicChatter @OpenAcademics Second, it is your PhD, but the lab's project. You should aim to become the intellectual leader of the project after around a year, but always lead with humility. Others around you will always know more than you on specific techniques or domain knowledge. 3/n
Read 21 tweets

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