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Monocytes Differentiated with IL-15 Support Th17 and Th1 Responses to Wheat Gliadin

Celiac.com 03/10/2010 - A team of researchers recently observed that monocytes differentiated with IL-15 support Th17 and Th1 responses to wheat gliadin. They discuss the implications of this discovery for celiac disease in a recent article in Clinical Immunology.

The research team included K. M. Harris, A. Fasano, and D. L. Mann of the Pathology Department at the University of Maryland School of Medicine.

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It is understood that interleukin (IL)-15 contributes to the immuno-pathogenesis of celiac disease. However, the effect of IL-15 on APC that shape adaptive immune responses to gliadin is not well understood. Using PBMC from healthy individuals, the team demonstrated that monocytes differentiated with IL-15 (IL15-DC) produced IL-1beta, IL-6, IL-15, IL-23, TNFalpha and CCL20 in response to pepsin-trypsin digested gliadin (PTG) and activated contact-dependent Th17 and Th1 responses from autologous CD4(+) T cells.

Compared with control subjects, PBMC from celiac disease patients showed lower concentrations of IL-15 augmented IFNgamma responses to PTG. So, by generating IL15-DC, IL-15 supports Th17 and Th1 responses to a dietary antigen that produces no such responses in healthy individuals. The team notes that IL-15 hypersensitivity may cause these potentially pathogenic immune responses to develop in celiac patients, but not in healthy individuals.

They conclude that the pathogenesis of celiac disease is likely due in part to genetic and/or environmental factors that control IL-15 expression and responsiveness in the gut.

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By the way, I got my biopsy pathology report and the doctor took 2 biopsies, not the recommended 4-6. It says no "significant villous blunting not seen." I don't know if I should laugh or cry---so frustrating.

Thank you, this does feel helpful and reassuring. Did you end up getting blood tests again after going gluten-free? Do you have to worry about cross contamination as much as with a celiac diagnosis? How do you explain it to friends and family? Non-Celiac gluten sensitivity sounds so vague and I know it's dumb, but I worry about people not taking me seriously.

Helen, a woman with severe lifelong eczema/dermatitis, wrote to me a few weeks ago, saying "I have taken your advice and been strictly gluten free for five months now. The eczema inflammation is 99% gone and my skin quality has significantly improved. I do still get a bit itchy around my neck area and elbow creases, more so at night when it is warm. I have noticed a significant improvement in my asthma also. I still use antihistamines perhaps once or twice a week for runny nose. Does this mean I will need to be gluten free for life? Which of your books would you say would be the most relevant for someone in my position? Thank you for your assistance, regards, Helen. View the full article

Hello and welcome Reading your post it looks like each of your results were within the 'normal' range. There doesn't appear to be mention of a total serum IGA to make sure you have enough of this to begin with to make the test accurate however - but there are others here who are more experienced who may be able to tell you more. There are some other celiac tests: tTG IgA and tTG IgG -DGP IgA and DGP IgG -EMA IgA -total serum IgA and IgG (control test to ensure tests are not false negatives) They may not be covered by your provider however. Note that you appear to have been avoiding gluten somewhat already, that could impact on the tests accuracy. Your symptoms sound like they could be gluten related (but then practically everything could!) but you may want to discuss with your doctor whether to push for further testing or move to trial gluten free diet. Some people, like myself, test negative but still find symptoms respond to gluten free. Best of luck!

There's a great post by Tarnalberry in that thread.