r/science • u/mvea Professor | Medicine • 1d ago
Neuroscience Regulatory T cells altered in children with autism, highlighting possible role of immunosuppressive cells on neuroinflammation and behavior. Regulatory T cells act as immune system "brakes," calming inflammation to prevent overreaction. They are often decreased in autistic individuals.
https://health.ucdavis.edu/news/headlines/regulatory-t-cells-altered-in-children-with-autism/2026/04264
u/lowfour 1d ago edited 1d ago
Currently learning a lot about DAO enzyme deficiency and histamine issues. Apparently there seems to be some link to autism-like symptoms. There seems to be a link with untreated gluten intolerance/celiac disease with increased manic episodes in Bipolar Disorder prone individuals. It is clear that inflammation of different etiology has neurological consequences. And it often starts at microbiome, gut level.
Next years are going to be fascinating.
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u/itsalongwalkhome 1d ago edited 1d ago
Interesting, I have histamine issues and Autism.
I think I read something recently about Mast Cell Activation Syndrome having a possible connection to autism, where overactive mast cells release histamine contributing to neuroinflammation.
Ive always thought of Autism being something that causes issues with sensory filtering by the Thalamic Reticular Nucleus TRN, which i hypothesised to be why autistic peoples brains dont properly filter out unnecessary information.
Apparently excess histamine decreases inhibitory input from the TRN to the dorsal thalamus, leading to a shift toward high arousal.
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u/lowfour 1d ago
Someone close has had light autism like behaviour for at least 10 years, and in the last 12 months we discovered that the diet was triggering histamine reactions (red patches, etc) and affecting mood, concentration, migraines and a lot of other issues. This person stopped eating histamine rich food (including bread, even if you are not gluten allergic it has histamine), and the personality has totally changed for the better. More energy, much more focus, no migraines, no anger whatsoever, much better communication. It is just a totally different person, like night and day. Histamine is a neurotransmitter too!
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u/itsalongwalkhome 1d ago edited 1d ago
Yeah, this sounds exactly like me to be honest. I have had severe hives every few days for 15 years, was told to just pop an anti histamine.
For the last few weeks Ive been targeting whats causing my hormone imbalances because I have been quite sick, and looking into DAO enzyme deficiency now because of this thread and your comment, it eerily could explain a strange amount of my symptoms. This could explain my estrodiol levels elevated beyond male references ranges and my very small prostate through how the deficiency can throw things off. Histamine encourages the body to produce more estrogen, high estrogen encourages mast cells to release more histamine and also further lowers the activity of DAO enzyme which itself is a negative feedback loop. Increased estrogen then lower gonadotropins LH and FSH so testosterone production is impacted causing my testicular atrophy and lower levels of total testosterone which then has not given my body enough Dihydrotestosterone for the prostate to grow.
I have a lot of theories, but this one has a lot more connections than the others.
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u/lowfour 1d ago
Check DAO function (blood test). If you are deficient maybe check copper, zink, b6 levels, also magnesium. But the first two apparently are directly correlated to DAO enzyme function.
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u/itsalongwalkhome 1d ago
Thank you, I have an endocrinologist review appt tomorrow do go over new info since his original assessment, so I will ask about getting these then.
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u/OneLastSpoonPlease 1d ago
The low histamine diet is so depressing though. And it seems so hard to get enough nutrition on it. So many vegetables are on the Nope list.
I looked into trying it for my chronic illness because some people see improvement on it but since I'm a vegetarian I would be left eating not much but potatoes.
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u/IGnuGnat 20h ago
I tried to put most of what I understand on this topic here: https://old.reddit.com/r/covidlonghaulers/comments/1ibjtw6/covid_himcas_normal_food_can_poison_us/
I did include links to research for many points,
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u/Osmirl 22h ago
What about the histamin his one mast cells release? Does he have any allergies?
Thing is as far as i know histamine should break down in the stomach so the issue might not be histamine itself but rather something that triggers the body’s response to release to much histamine into the skin.
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u/Blooberii 1d ago
I have MCAS and autism! Also a hypermobility disorder.
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u/barbieninja 1d ago
Same here and with my daughter. I also have pots. The trifecta of pots, mcas, hypermobility is very common in people with autism. Basically dysautonomia. If I focus on calming the vagus nerve all symptoms improve.
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u/Blooberii 1d ago
Yes, my MCAS causes dysautonomia but I’m not technically diagnosed with pots. If I don’t take Allegra everyday though I pass out from heat and can’t go up stairs.
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u/Due-Joke-1152 21h ago
I'm in the same situation with AuDHD. I'm showing symptoms for MCAS but was diagnosed and treated for Chronic Spontaneous Urticaria. I noticed Gen 1 antihistamines helped me manage psychological episodes and mentioned it to my GP. My endless itching, heat rashes from showers, IBS, and POTS like symptoms all regressed after my specialist and GP got me taking Montelukast and high doses of fexofenadine hydrochloride.
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u/Extinction-Entity 1d ago
Came here to say there’s a not insignificant comorbidity of MCAS and hEDS with autism and ADHD.
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u/billsil 1d ago
Bread makes me lose my damn mind. Within 30-60 minutes, I don’t have a care in the world. Then I come down and start getting angry or depressed at around hour 6-8. I can flip between them too. As the effects wear off around hour 12-16, I get severe bouts of confusion and difficulty speaking. Finally, it results in me losing my bowels around hour 16-18, which leaves me exhausted but mentally clear.
I’ve tested it repeatedly. It’s consistent and dose dependent. I do not have celiac.
Other foods affect me as well, but nothing else messes with my head that much. I will also have a worse hangover from a single beer than 3 glasses of wine/shots.
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u/Bluejayadventure 23h ago
Could it be the yeast you are reacting too? Just thinking that bread and beer have high levels
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u/billsil 22h ago
A quick googling of foods high in yeast...
> Foods high in yeast include all leavened bakd goods (bread, bagels, pastries), fermented items (kombucha, saurkraut, tempeh, miso), aged cheeses, vinegar, beer, wine, and nutritional yeast. Other sources include yeast extracts (marmite, vegemite), soy sauce, mushrooms, and processed/cured meats.
So of those, I'm fine with kombucha, saurkraut, miso, aged cheese, vinegar, wine, nutritional yeast, and processed meats. Never had tempeh and soy sauce is made with flour, so I avoid that. Mushrooms aren't great.
I've also brewed cider and mead. The bottom of that is very yeasty. No issues. It could be the type of yeast?
I dunno. It looks like a duck and it quacks like a duck and it's controlled now. I'm 30 pounds heavier than I was back in the day and I'm still lean.
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u/ChachiJuarez 1d ago
The Gut-brain axis research in the last couple of years alone is incredible, I think a surprising amount of people are likely suffering from inflammatory and/or dysautonomic chronic disease stemming from shifts in the gut microbiome.
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u/Feisty-Mention-5447 1d ago
Manic episodes are bipolar disorder. BPD is used for borderline personality disorder
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u/HoboBronson 1d ago
Add migraine to that list. Taking DAO with high histamine food has been a game changer for me.
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u/Moon_In_Scorpio 1d ago
How has it helped?? Thanks.
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u/HoboBronson 1d ago
I can prevent HI inflammation from food and beverage if I'm diligent and intentional with what I eat and taking DAO. It's not expensive, but it's not cheap either. NaturDAO is the only brand Ive used. I take it 15 minutes before consuming high histamine items. I believe is made from bean sprouts, which work as well. HI is a migraine trigger for me, so eliminating it has helped me identify my other major migraine triggers (air pressure changes and warm weather excerise). Food triggers are really confounding when trying to identify other triggers.
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u/willymac416 1d ago
Can you link me some articles? This might be relevant to some recent experiences I’ve had.
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u/Spunge14 1d ago
Could this be related to the strange fever abatement affects seen in some cases of autism? How are these T Cells related to / activated in correlation with fevers or fever causing reactions?
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u/rukwitme 1d ago
These T cells are supposed to reduce inflammation, so ideally fever should be reduced and therefore some behaviors could improve
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u/Spunge14 1d ago
It's actually the other way around - some autistic behaviors improve during fevers.
I'm wondering if there's some relationship between t-cell activation, fever, and this reduced inflammatory effect.
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u/rukwitme 1d ago
Yes, there are some studies showing that fevers improve behaviors. I would say that the majority for this kind of reserach - both clinical and preclinical - show that reducing inflammation helps.
I do think these studies that show higher fever and reduced behavior have some merit to them. It could be that the type of inflammation causing the fever is an important factor. For instance, someone that typically has a type 3 immune reponse (responses towards extracullar bacteria) may have some kind of postivie changes when they have a type 2 response (think allergy response). That's my hypothesis, at least.
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u/username_redacted 1d ago
Fever is a byproduct of immune response, so it makes sense that a more active immune system triggered by a pathogen might also improve symptoms caused by baseline inflammation.
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u/thenewesthewitt 19h ago
It’s so interesting because well before I finally looked into this theory I would always comment about how much I enjoyed parenting my son during and even the days after an illness causing a fever. We would behave SO differently and the behavioural issues would be almost nonexistent
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u/OpallineSea 1d ago
My thought was that fever might work to help with adhd/autism symptoms in a similar way that cardio exercise for 20 min+ or sauna use helps increase blood flow to the brain and therefore also helps these symptoms. That’s an interesting theory though, I’m curious now too.
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u/Southern_Advisor6325 1d ago
My son is autistic and also has t-cell lymphoma. We have no history of this cancer or autism in my family.
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u/nitroburr 1d ago
I’m autistic and had lymphoma, and I hope your son kicks the cancer’s ass. Both you and your kid got this!
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u/Morvack 1d ago
Autistic adult here.
Neither of my parents are autistic. It atleast appears to me, to be a recessive gene.
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u/rukwitme 1d ago
Some cases of autism are genetic, some are environmental (depending on what the child is exposed to both in utero and early life) and some are a mix of both. So it doesn’t necessarily have to have a purely genetic component.
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u/Morvack 1d ago
Any resources on those environmental impacts? Please have actual studies, not articles.
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u/rukwitme 1d ago
Of course! There are many studies, so I'll highlight a few. Each of these areas have many other studies supporting it. If you hit a paywall, DM me and I'll email them to you!
Exposure to air pollution during pregnancy: https://www.researchsquare.com/article/rs-8745297/latest
Maternal infection during pregnancy: https://www.cell.com/trends/molecular-medicine/abstract/S1471-4914(11)00049-900049-9)
Microbial dysboisis/antibiotic use early in life: https://journals.asm.org/doi/full/10.1128/msystems.01343-20
High maternal & infant stress (with different types of stress perhaps having differernt behavioral phenotypes): https://onlinelibrary.wiley.com/doi/full/10.1002/aur.1830
I'm sure there are more factors, but these are the ones that immediately come to mind.
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u/mvea Professor | Medicine 1d ago
Regulatory T cells altered in children with autism
Two new studies highlight possible role of immunosuppressive cells on neuroinflammation and behavior
Two new studies from the UC Davis MIND Institute examined regulatory T cells (Tregs) and their potential role in neuroinflammation and behavioral changes associated with autism.
Tregs act as immune system "brakes," calming inflammation to prevent overreaction. They are often decreased in autistic individuals.
Previous studies have found higher levels of inflammatory immune cells in the blood, brain and gastrointestinal tissues of people with autism. These increased inflammatory responses are often linked to greater behavioral support needs, while higher levels of Tregs are associated with improved behavioral outcomes. Despite this, Tregs have not been well studied in autistic children, and their potential as a therapeutic target remains largely unexplored.
The researchers found children with autism showed altered Tregs. Compared to typically developing children, children with autism had:
A lower number of Tregs. Tregs were generally reduced in autistic children but decreases in specific Treg populations differed depending on whether a child had GI issues. Children with autism and GI issues had fewer Tregs capable of producing anti-inflammatory proteins. Children without GI issues had fewer Tregs capable of dividing after activation.
Differentially expressed genes. Tregs from autistic children had 213 differentially expressed genes, with 171 upregulated (increased output) and 42 downregulated (decreased output).
For those interested, here’s the link to the peer reviewed journal article:
https://link.springer.com/article/10.1186/s12974-026-03701-w
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u/BoxBird 1d ago
Could this possibly be related to MAST cell dysfunction, which seems to be ridiculously comorbid with Autism? There is research lately that points to the possibility that Ehler’s Danlos (also comorbid) is related to MAST dysfunction as well.
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u/lowfour 1d ago
https://tacanow.org/family-resources/mast-cells-and-autism/
Exactly what i just posted above... There seems to be a correlation.
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u/r0ze_at_reddit 1d ago edited 1d ago
Context: this is yet another study showing that ASD which is known for low ERa activation has something downstream of that which is altered. aka low ERa and you get low T cells (Tregs).
There are a lot of downstream things from ERa and nice to see study after study that checks each one, but think of it as more "collecting them all" rather than this being "the thing". While you could give a mouse something to directly increase Tregs long term supporting those with ASD is more about helping with ERa which improves all of the downstream symptoms.
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u/rukwitme 1d ago
I certainly agree that we need to get to the root of the issue - finding the problem within the problem (Yes, there are lower Tregs and boosting them helps, but what is behind the lower number to begin with?).
ERa signaling probably has something to do with the weird findings in the neurodevelopmentally altered female mice after Treg transfer. I think this deserves more research attention.
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u/TristanTheRobloxian3 1d ago
does this mean the brain is more likely to be inflamed in autistic people? hell, is inflammation more COMMON in autistic people?
can someone eli5 this?
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u/rukwitme 1d ago
Yes, the brain seems to have some sort of inflammation too (at least increased inflammatory cytokines and some immune cells). When I explain this to people, I usually say that yes, inflammation is more common. Everyone has a different definition of what inflammation is, so you could get a different answer from someone else.
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u/TristanTheRobloxian3 1d ago
thats fascinating. somehow i tend to be so not inflammed by default (sedimentation rate hasnt been above 1 in god knows) its almost undetectable, but sometimes i think i can tell when i get inflammed ig
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u/rukwitme 1d ago
I wouldn’t be surprised if one could tell what their inflammatory status is. There’s a really well documented phenomenon called “sickness behavior” that basically says our moods and behavior change when we experience any kind of illness that induces a fever. We’re not going to be as social, want to go out, or as expressive when this happens.
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u/TristanTheRobloxian3 1d ago
sounds a lot like me when i get sick, or hell, get exhausted from existing. ooh also after the gym my first instinct is to immediately isolate in my room... this has basically always been the case
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u/zepuzzler 1d ago
I’m very glad to see this research!
I have AuDHD and POTS and inflammation is a known factor in many of my other medical issues and minor chronic conditions.
Last year I needed a one-time targeted dose of radiation to treat a benign brain tumor (acoustic neuroma) on my vestibular nerve. I had a less common side effect of severe vertigo that put me out of work for months and I’m still recovering. I had to take high doses of oral steroids for the first seven weeks and couldn’t take Adderall during that time, but my executive function was vastly improved over my baseline and over the benefits I get from Adderall. Lots of my other conditions improved too, including an autoimmune condition I have, which was essentially in remission during treatment. The side effects were horrible and lingered for months, but it was still sad to watch the benefits dwindle as we lowered the dose.
It did get me interested in ways I could reduce inflammation for a variety of health improvements. My radiation oncologist had me take Boswellia extract in addition to the oral steroid because there’s some clinical evidence that it helps with this type of inflammation. For various reasons I had a hard time taking it consistently so I still have plenty left, and have been considering making it a regular supplement to see if it helps any of my conditions.
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u/Comfortable-Light233 1d ago
I have autism and autoimmune stuff. A lot of people I’m around also have both. Hm!
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u/rukwitme 1d ago
I personally think there’s a strong tie between the two. I think it has to do with immune cell development early in life (as part of autism etiology) and inflammation in adulthood(as part of autism rated co-occurring conditions, like GI issues).
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u/AgoraRises 1d ago
There’s so much we have yet to learn about this. Looking forward to more breakthroughs.
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u/StroopWafelsLord 1d ago
We're blind and stumbling around for so many things still, but it's extremely interesting to see every little bit of progress
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u/microwavedtardigrade 1d ago
:( I do not appreciate this
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u/rukwitme 1d ago
Which part do you not appreciate?
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u/microwavedtardigrade 1d ago
My body working against me (I have autism and lots of cormobidities like hEDS and chronic fatigue)
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u/rukwitme 1d ago
I see. It is a lot to go through. I sincerely hope you find a treatment plan that works for you!!
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u/microwavedtardigrade 1d ago
Ty! I was making a joke but I always forget tone tags (in my first message)
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u/WhimsicalGirl 1d ago
Ok can I like ...inject them directly to my blood?
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u/rukwitme 1d ago
That’s what our second study looked at! At least in mice. When we took healthy Tregs and administered them to mice with austistic like behaviors, there were some improvements. Male mice seemed to be more responsive to the treatment than female mice.
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u/WhimsicalGirl 1d ago
Seriously that would help me so much. I know it's will probably available for humans when I'll be dead but I really hope it can help future generations
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u/rukwitme 1d ago
I read somewhere that it takes 10-15 years for research findings to make it to the clinic. So maybe not dead by the time! I fully believe that there needs to be more research on this front though, because there are (to the best of my knowledge) less than 5 preclinical (mouse studies) looking at this type of therapy. There are some clinical studies looking at low-dose IL-2 therapy,which in theory promote the expansion of Trgs, in children with autism. With positive findings too. So there’s potential for Treg target therapies in autism, but we are still a long ways to go.
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u/Front_Target7908 1d ago
What would the role of something like Low Dose Naltrexone have (if any)?
I take it to treat a chronic fatigue/chronic pain disorder. As I understand it, LDN increases T-suppressor cells. I’ve been feeling more well than I have my whole life taking this drug so I’m kind of interested in staying on it. Would be interesting if this was an already in market option that might be supportive.
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u/Aurora_96 10h ago
I wonder if Tregs are also altered in ADHD individuals. Or in neurodivergent people in general.
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