No popular authors found.
Ads by Google:

Categories

No categories found.


Get Celiac.com's E-Newsletter





Ads by Google:


Follow / Share


  FOLLOW US:
Twitter Facebook Google Plus Pinterest RSS Podcast Email  Get Email Alerts
SHARE:

Popular Articles

No popular articles found.
Celiac.com Sponsors:

Gliadin Triggers Innate Immune Reaction in Celiac and Non-celiac Individuals

Celiac.com 12/31/2012 - In people with celiac disease, eating wheat, barley, or rye triggers inflammation in the small intestine. Left unchecked, this inflammation causes the gut damage that is associated with untreated celiac disease.

Photo: CC--barryskeatesSpecifically, the storage proteins in these grains (gluten) trigger an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition.

Researchers actually have a pretty good understanding of this aspect of celiac disease, part of a process called adaptive immunity.

However, there has been some research that suggests that gluten proteins might trigger an immune response in people who do not have celiac disease, and who do not carry the HLA-DQ2 or HLA-DQ8 genetic markers that predispose them to developing celiac disease. Such a response is part of a process called innate immunity, and is far less understood than the adaptive immunity process.

The innate immune system provides an early response to many microbial and chemical stimuli and is critical for successful priming of adaptive immunity.

To better understand the relationship between adaptive immunity and innate immunity in celiac disease, a research team recently set out to determine if gliadin digests might induce innate immune responses in celiac and non-celiac individuals.

Specifically, they wanted to know if wheat amylase trypsin inhibitors drive intestinal inflammation, and if so, by what receptor mechanism.

The research team included Yvonne Junker, Sebastian Zeissig, Seong-Jun Kim, Donatella Barisani, Herbert Wieser, Daniel A. Leffler, Victor Zevallos, Towia A. Libermann, Simon Dillon, Tobias L. Freitag, Ciaran P. Kelly, and Detlef Schuppan. They are affiliated variously with the Division of Gastroenterology and the Proteomics and Genomics Center at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston, with the Department of General Pediatrics and the Department of Internal Medicine I at the University Medical Center Schleswig-Holstein Kiel in Kiel, Germany, the Department of Experimental Medicine at the University of Milano-Bicocca in Milan, Italy, the German Research Center for Food Chemistry in Garching, Germany, the Hans-Dieter-Belitz-Institute for Cereal Grain Research in Freising, Germany, the Division of Molecular and Translational Medicine in the Department of Medicine I at Johannes Gutenberg University in Mainz, Germany, and with the Department of Bacteriology and Immunology at the Haartman Institute at the University of Helsinki in Finland.

A number of earlier studies (Molberg et al., 1998; Anderson et al., 2000; Shan et al., 2002) have found HLA-DQ2– and HLA-DQ8–restricted gluten peptides that trigger the adaptive immune response in people with celiac disease. However, only 2–5% of individuals who show these HLAs develop celiac disease, which means that other factors, especially innate immune activation, are at play in the generation of celiac disease.

Ads by Google:

Responsive innate cells are primarily macrophages, monocytes, DCs, and polymorphonuclear leukocytes that by means of their pattern-recognition receptors, such as TLRs, trigger the release of proinflammatory cytokines and chemokines, resulting in recruitment and activation of additional inflammatory cells (Medzhitov, 2007). Earlier studies (Maiuri et al., 2003) showed that peptides p31-43 or p31-49 from α-gliadin, that lack adaptive stimulatory capacity, triggered innate immune reactions by inducing IL-15 and Cox-2 expression in patient biopsies, and MHC class I polypeptide–related sequence A (MICA) on intestinal epithelial cells (Hüe et al., 2004).

However, these studies have proven difficult to reproduce in cell culture, and researchers could not identify any specific receptor responsible for the observed effects. In a subsequent study, gliadin, in cell culture, reportedly triggered increased expression of co-stimulatory molecules and the production of proinflammatory cytokines in monocytes and DCs (Nikulina et al., 2004; Cinova et al., 2007).

Two other studies (Thomas et al., 2006; Lammers et al., 2008) implicated the chemokine receptor CXCR3 in increased intestinal epithelial permeability upon gliadin challenge in a MyD88-dependent manner. However, those studies failed to reproducibly identify a specific gliadin peptide as the trigger.

So far, no clear picture of the role of the innate immune system in celiac disease has emerged. In this study, the researchers show that members of the non-gluten α-amylase/trypsin inhibitors (ATIs), CM3 and 0.19, pest resistance molecules in wheat and related cereals, are strong triggers of innate immune responses in human and murine macrophages, monocytes, and dendritic cells.

Their results show that ATIs activate the TLR4–MD2–CD14 complex and lead to up-regulation of maturation markers and elicit release of proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients’ biopsies.

They also show that mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs.

These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders.

The findings of this study mean that the proteins in wheat may trigger immune reactions not just in people with celiac disease, but in people without celiac disease, and that these reactions may be actively contributing to the development of numerous other intestinal and non-intestinal immune disorders. That's a pretty big deal. Stay tuned to see how future studies elaborate these findings.

Read the entire study in the Journal of Experimental Medicine.

Source:

Celiac.com welcomes your comments below (registration is NOT required).












Related Articles



1 Response:

 
anthony oldfield
Rating: ratingfullratingfullratingfullratingfullratingfull Unrated
said this on
16 Feb 2013 3:56:36 PM PDT
Innate immune system in trouble.




Rate this article and leave a comment:
Rating: * Poor Excellent
Your Name *: Email (private) *:




In Celiac.com's Forum Now:


Yeah I need someone to attend with me, I had someone else but they canceled on me. The hotel room is booked from the 16th-20th of August. I can pick up from the airport, greyhound, or train station and drop off if need be, room is booked from the 16th technically a day before the convention so yo...

No anti-sm(lupus)? Yes, anti dsDNA is for SLE(lupus). No ENA panel,anti-RNP, anti-SS-A, anti-SS-B, anti histone, scl-70, etc? I'd ask for a referral, if you feel that there is something going on. I think that would be a logical step because of the positive ANA and lack of investigation. 1:640 is ...

My MCH is always high too. Have some other oddities but doc always say labs are great as well. I dont think they ever really bother with the MCH. I'm also in testing and showed negative on the same ones you did. My IGA is fine though. As far as the other tests, maybe your girls GI can order or yo...

Hi there! I follow a low histamine diet that Cycling Lady brought to my attention a long time ago. Citrus fruits and their juices are histamine releasing foods. High histamine levels can cause hives just like in an allergic reaction. Here's a helpful site: https://www.histaminein...

Thank you! Exactly!