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IL-15 Allows Inflammation in Celiac Guts by Suppressing the Immunosuppressive Effects of Treg Cells


Celiac.com 06/06/2011 - The interplay among the different immune cells mediating intestinal inflammation in celiac disease is complicated indeed. A subset of T regulatory (Treg) cells that express the Foxp3 protein are present in higher numbers in the intestines of patients with active celiac disease than in healthy controls. Treg cells act to suppress the immune system, providing tolerance to self-antigens. A recent report in the American Journal of Gastroenterology demonstrates that these cells proliferate upon the ingestion of gluten in order to suppress an overactive inflammatory response, but that their suppression is in turn suppressed by interleukin-15.

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First they confirmed that there is in fact increased expression of Foxp3+ cells in the intestinal mucosa of untreated celiac patients; happily, they write that "no significant differences were noted in the number of Foxp3+ cells in biopsy samples of treated celiac disease in comparison with biopsy samples of non-celiac disease controls." Next, they used an in vitro gliadin challenge system - no celiac patients were harmed during the course of this study! - to see if the increase in this cell population was dependent on gliadin, and it was. T cells are so named because they are made in the thymus; this demonstration that they can originate in the small intestine lamina propria is interesting. Treg cells are generally immunosuppressive, and the Treg cells isolated from celiac guts demonstrated this immunosuppressive ability in vitro. So the researchers wondered: why is there still so much inflammation in untreated celiac disease patients? They found that the cytokine IL-15 could suppress the proliferation of Treg cells, and completely shut down their ability to produce interferon gamma (IFN- γ ). This is at least partially because Treg cells from celiac patients turn out to have a significantly higher surface density of receptors for IL-15 than Treg cells from healthy controls, rendering them more sensitive to IL-15's effects.

Zanzi et al bolstered their findings by achieving the same results using two independent experimental methods. It is not yet clear how IL-15 impairs the suppressive activity of Treg cells. But these scientists are actively working on it.

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Vegetarian here too, celiac really makes it tough as all the Quorn meat replacement products bar the odd one or two are out Then there's all the scare sites saying only paleo type diets will repair your insides but guess what they're all heavily meat / fish based. @Ennis_TX has some good ideas for meals

Wow guys just read all the replies Thankyou all so much!!! There are so many things you've all said that has triggered a light bulb in my little head! The glasses may not be clean!! I will put this to a test. One night I'll stick to bottles of cider (double checked are gluten-free) another I'll try the Gin or William chase vodka if I can find it! And see the effects. if I loose many days due to these not working I'll see a practitioner and see what the deal is! Before I was diagnosed at Coeliac... I went to a herbalist who did a test and said corn is funny on my body!!! But then 18months later (when I became incontinant and lost a lot of weight) my bloods came back positive (after begging the docs and telling them it wasn't IBS) i don't tend to snack at bars on food but I must admit I never thought it could be the way it's served!! The humour and information has made me feel so much better thanks all xxx

Hey Matt thanks for your reply fellow Brit! I this is very interesting... I am very sensitive to cross contamination... e.g. A sieve wasn't washed properly when I lived at my mums so when I had drained my gluten-free pasta .. I hadn't even eaten the dish before I started to pass out and go dizzy and hot .. calling for my bf and mum ( they had a great team going when I would have an episode) it's horrendous! The fatigue is something I imagine every coeliac suffers with! I have to nap a lot. Ok so the booze I drink most of is -processo -amaretto -vodka, wine, cider (very rarely) when I drink at home I'm fine!!! I wonder if it's cross contamination from the bar or the level of alcohol?! I also had a jger bomb shot on Friday (looked it up and a lot of people say it's gluten-free) it's a hard live but someone's got to do it!! Thanks for the reply! When you get poorly from gluten (and the other evil candidates) are you so bad you can't function and feel your body is about to snap? Kind regards steph

Hi Steph and welcome I'm yet another Brit, funny how the alcohol threads flush us out I don't drink now but after a big night I used to get truly savage all day hangovers, much worse than those of my friends. They could include splitting headaches, vomiting, nausea, a 'fuzziness' in my head, sweats etc. After I put the pieces together and went gluten free I had a 'big night' on cider only and the next day was a revelation. What I'd thought was a 'normal' hangover was, for me at least, anything but. With gluten out of the equation hangovers were a breeze! The difference was mind blowing and just one more example of how gluten had been messing with me over the years. So when I read your post my first thought was that there was some trace gluten contamination going on. However: Obviously you've been at the diet for some considerable time now and know the score. I know Coeliac UK are firmly of the opinion that all spirits are safe but some (note some this a contentious one :D) members here will tell you they react to gluten based grain spirits for instance which distillation should render safe. Then there's the dangers of shared lines if you're drinking say Strongbow in a pub as alluded to above. Lastly it its wine, there's the often cited but maybe apocryphal these days 'flour to seal the casks' possibility. Finally there's bar snacks, maybe a brand of nuts etc that you snack on that may have changed their production process? I'm sure you've thought of these already, but it may be useful if you post your alcoholic drink choices / bar snack of choice up here maybe someone will have some input?. The second thing which leapt out was: Would you class yourself as super sensitive to cross contamination etc? Firstly that would make the cross contamination theory more compelling. You could test that out by having a drink at home under controlled circumstances to see whether the same issue arises? That could also answer the quantity question. Does one safe drink trigger it, two, three etc? Finally, and this is one that I find difficult, knowing you have the gluten issue may lead you to assume it's that when it could be something else. I tend to attribute EVERYTHING in the world to gluten these days due to it being able to affect me in so many different ways. Crisis in Korea? Gluten. Russian tanks massing on the Ukrainian border? Check their wheat intake. Global warming? etc. So it may make sense to pursue some other ideas at the same time. Try: http://goaskalice.columbia.edu/answered-questions/suddenly-drinking-alcohol-makes-me-sick http://www.steadyhealth.com/topics/very-abnormal-hangovers-thinking-it-could-be-allergy-to-alcohol and a doctor's answer: http://www.steadyhealth.com/medical-answers/abnormal-reactions-to-alcohol Cheers Sorry, best of luck! Matt

Similarly, I've been vegetarian for 25+ years. A 2015 Nature study connecting emulsifiers with microbiome changes has me wondering about the processed foods that I ate in the past, and I wonder about the wisdom of eating as much seitan as I did. I mostly prefer my post-diagnosis diet since it forces me to consider every ingredient and to cook from scratch more.