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Celiac Disease & Gluten-Free Diet Forums

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Celiac Disease & Gluten-Free Diet Blogs

  • kareng's Blog
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  • Trials and Tribulations
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  • Research on South African Celiac Tours
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  • Melissa.77's Blog
  • Keating's Not-so-Glutenfree life
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  • Coeliac, or just plain unlucky?
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  • Scott's Celiac Blog
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  • Searchin for a Primary Care Dr. In Redlands That is Knowledgeable about Celiac disease
  • num1habsfan's Blog
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  • Celiac-Positive
  • Jason's Mommy's Blog
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  • I love my plant Cactus <3
  • Chele's Blog
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  • Blues Boulevard
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  • Michael Fowler's Blog
  • Living in Japan with Ceoliac Disease
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  • MJ
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  • HONG KONG GLUTEN, WHEAT FREE PRODUCTS
  • Guth 101's Blog
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  • Gail Marie's Blog
  • Healthy Food Healthy You
  • SydneyT1D - Diabetic and Celiac YouTuber!
  • GFGF's Blog
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  • SMAS: www.celiac.com
  • gardener1's Blog
  • Naezer's Blog
  • JordanBattenSymons' Blog
  • JillianC
  • Sugar's Blog
  • Blanche22's Blog
  • Jason's Blog
  • Gluten-Free Sisters :)
  • Eab12's Celiac Blog
  • ohiodad's Blog
  • Newly Self Diagnosed?
  • misscorpiothing's Blog
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  • Petroguy
  • abqrock's Blog
  • WhoKnew?'s Blog
  • Soap Opera Central
  • nurcan's Blog
  • Cindy's Blog
  • Daughter_of_TheLight's Blog
  • nopastanopizza's Blog
  • w8in4dave's Blog
  • Mr J's Blog
  • Rachel Keating's Blog
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  • krisb's Blog
  • deetee's Blog
  • CAC's Blog
  • EmilyLinn7's Blog
  • Teri Kiefer's Blog
  • happyasabeewithceliac's Blog
  • quietmorning01's Blog
  • jaimekochan's Blog
  • Cheryl
  • Seosamh's Blog
  • donna mae's Blog
  • Colleen's blog
  • DawnJ's Blog
  • Gluten Challenge
  • twins2's Blog
  • just trying to feel better's Blog
  • Celiac Teen
  • MNBelle blog
  • Gabe351's Blog
  • moosemalibu's Blog
  • Coeliac Disease or Coeliac Sprue or Non Tropical Sprue
  • karalto's Blog
  • deacon11's Blog
  • Nyxie's Blog
  • Swpocket's Blog
  • threeringfilly's Blog
  • Madison Papers: Living Gluten-Free in a Gluten-Full World
  • babinsky's Blog
  • prettycat's Blog
  • Celiac Diagnosis at Age 24 months in 1939
  • Sandy R's Blog
  • mary m's Blog
  • Jkrupp's Blog
  • Oreo1964's Blog
  • keyboard
  • Louisa's Blog
  • Guts & Brains
  • Gluten Free Betty
  • Jesse'sGirl's Blog
  • NewMom's Blog
  • Connie C.'s Blog
  • garden girl's Blog
  • april anne's Blog
  • 4xmom's Blog
  • benalexander60's Blog
  • missmyrtle's Blog
  • Jersey Shore wheat no more's Blog
  • swezzan's Blog
  • aheartsj's Blog
  • MeltheBrit's Blog
  • glutenfreecosmeticcounter
  • Reasons Why Tummy tuck is considered best to remove unwanted belly fat?
  • alfgarrie's Blog
  • SmidginMama's Blog
  • lws' Blog
  • KMBC2014's Blog
  • Musings and Lessons Learned
  • txwildflower65's Blog
  • Uncertain
  • jess4736's Blog
  • deedo's Blog
  • persistent~Tami's Blog
  • Posterboy's Blog
  • jferguson
  • tiffjake's Blog
  • KCG91's Blog
  • Yolo's Herbs & Other Healing Strategies
  • scrockwell's Blog
  • Sandra45's Blog
  • Theresa Marie's Blog
  • Skylark's Blog
  • JessicaB's Blog
  • Anna'sMommy's Blog
  • Skylark's Oops
  • Jehovah witnesses
  • Celiac in Seattle's Blog
  • March On
  • honeybeez's Blog
  • The Liberated Kitchen, redux
  • onceandagain's Blog
  • JoyfulM's Blog
  • keepingmybabysafe's Blog
  • To beer, with love...
  • nana b's Blog
  • kookooto's Blog
  • SunnyJ's Blog
  • Mia'smommy's Blog
  • Amanda's Blog
  • jldurrani's Blog
  • Why choosing Medical bracelets for women online is the true possible?
  • Carriefaith's Blog
  • acook's Blog
  • REAGS' Blog
  • gfreegirl0125's Blog
  • Gluten Free Recipes - Blog
  • avlocken's Blog
  • Thiamine Thiamine Thiamine
  • wilbragirl's Blog
  • Gluten and Maize-Free (gluten-free-MF)
  • Elimination Diet Challenge
  • DJ 14150
  • mnsny's Blog
  • Linda03's Blog
  • GFinDC's Blog
  • Kim UPST NY's Blog
  • cmc's Blog
  • blog comppergastta1986
  • JesikaBeth's Blog
  • Melissa
  • G-Free's Blog
  • miloandotis' Blog
  • Confessions of a Celiac
  • Know the significance of clean engine oil
  • bobhayes1's Blog
  • Robinbird's Blog
  • skurtz's Blog
  • Olivia's Blog
  • Jazzdncr222's Blog
  • Lemonade's Blog
  • k8k's Blog
  • celiaccoach&triathlete's Blog
  • Gluten Free Goodies
  • cherbourgbakes.blogspot.com
  • snow dogs' Blog
  • Rikki Tikki's Blog
  • lthurman1979's Blog
  • Sprue that :)'s Blog
  • twinkletoes' Blog
  • Ranking the best gluten free pizzas
  • Gluten Free Product
  • Wildcat Golfer's Blog
  • Becci's Blog
  • sillyker0nian's Blog
  • txplowgirl's Blog
  • Gluten Free Bread Blog
  • babygoose78's Blog
  • G-freegal12's Blog
  • kelcat's Blog
  • Heavy duty 0verhead crane
  • beckyk's Blog
  • pchick's Blog
  • NOT-IN-2gluten's Blog
  • PeachPie's Blog
  • Johny
  • Breezy32600's Blog
  • Edgymama's Gluten Free Journey
  • Geoff
  • audra's Blog
  • mfrklr's Blog
  • 2 chicks
  • I Need Help With Bread
  • the strong one has returned!
  • sabrina_B_Celiac's Blog
  • Gluten Free Pioneer's Blog
  • Theanine.
  • The Search of Hay
  • Vanessa
  • racecar16's Blog
  • JCH13's Blog
  • b&kmom's Blog
  • Gluten Free Foodies
  • NanaRobin's Blog
  • mdrumr8030's Blog
  • Sharon LaCouture's Blog
  • Zinc, Magnesium, and Selenium
  • sao155's Blog
  • Tabasco's Blog
  • Amanda Smith
  • mmc's Blog
  • xphile1121's Blog
  • golden exch
  • kerrih's Blog
  • jleb's Blog
  • RUGR8FUL's Blog
  • Brynja's Grain Free Kitchen
  • schneides123's Blog
  • Greenville, SC Gluten-Free Blog
  • ramiaha's Blog
  • Kathy P's Blogs
  • rock on!'s Blog
  • Carri Ninja's Blog
  • jerseygirl221's Blog
  • Pkhaselton's Blog
  • Hyperceliac Blog
  • abbiekir's Blog
  • Lasister's Thoughts
  • bashalove's Blog
  • Steph1's Blog
  • Etboces
  • Rantings of Tiffany
  • GlutenWrangler's Blog
  • kalie's Blog
  • Mommy Of A Gluten Free Child
  • ready2go's Blog
  • Maureen
  • Floridian's Blog
  • Bobbie41972's Blog
  • Everyday Victories
  • Intolerance issue? Helpppp!
  • Feisty
  • In the Beginning...
  • Cheri46's Blog
  • Acne after going gluten free
  • sissSTL's Blog
  • Elizabeth19's Blog
  • LindseyR's Blog
  • sue wiesbrook's Blog
  • I'm Hungry's Blog
  • badcasper's Blog
  • M L Graham's Blog
  • Wolicki's Blog
  • katiesalmons' Blog
  • CBC and celiac
  • Kaycee's Blog
  • wheatisbad's Blog
  • beamishmom's Blog
  • Celiac Ninja's Blog
  • scarlett54's Blog
  • GloriaZ's Blog
  • Holly F's Blog
  • Jackie's Blog
  • lbradley's Blog
  • TheSandWitch's Blog
  • Ginger Sturm's Blog
  • The Struggle is Real
  • whataboutmary's Blog
  • JABBER's Blog
  • morningstar38's Blog
  • Musings of a Celiac
  • Celiacchef's Blog
  • healthygirl's Blog
  • allybaby's Blog
  • MGrinter's Blog
  • LookingforAnswers15's Blog
  • Lis
  • Alilbratty's Blog
  • 3sisters' Blog
  • MGrinter's Blog
  • Amanda
  • felise's Blog
  • rochesterlynn's Blog
  • mle_ii's Blog
  • GlamourGetaways' Blog
  • greendog's Blog
  • Tabz's Blog
  • Smiller's Blog
  • my vent
  • newby to celiac?'s Blog
  • siren's Blog
  • myraljo's Blog
  • Relieved and confused
  • carb bingeing
  • scottish's Blog
  • maggiemay832's Blog
  • Cristina Barbara
  • ~~~AnnaBelle~~~'s Blog
  • nikky's Blog
  • Suzy-Q's Blog
  • mfarrell's Blog
  • Kat-Kat's Blog
  • Kelcie's Blog
  • cyoshimit's Blog
  • pasqualeb's Blog
  • My girlfriend has celiacs and she refuses to see a doctor
  • Ki-Ki29's Blog
  • mailmanrol's Blog
  • Sal Gal
  • WildBillCODY's Blog
  • Ann Messenger
  • aprilz's Blog
  • the gluten-free guy
  • gluten-free-wifey's Blog
  • Lynda MEADOWS's Blog
  • mellajane's Blog
  • Jaded's Celiac adventures in a non-celiac world.
  • booboobelly18's Blog
  • Dope show
  • Classic Celiac Blog
  • Keishalei's Blog
  • Bada
  • Sherry's blurbs
  • addict697's Blog
  • MIchael530btr's Blog
  • Shawn C
  • antono's Blog
  • Undiagnosed
  • little_d's Blog
  • Gluten, dairy, pineapple
  • The Fat (Celiac) Lady Sings
  • Periomike
  • Sue Mc's Blog
  • BloatusMaximus' Blog
  • It's just one cookie!
  • Kimmy
  • jacobsmom44's Blog
  • mjhere's Blog
  • tlipasek's Blog
  • You're Prescribing Me WHAT!?!
  • Kimmy
  • nybbles's Blog
  • Karla T.'s Blog
  • Young and dealing with celiacs
  • Celiac.com Podcast Edition
  • LCcrisp's Blog
  • ghfphd's allergy blog
  • https://www.bendglutenfree.com/
  • Costume's and GF Life
  • mjhere69's Blog
  • dedeadge's Blog
  • CeliacChoplin
  • Ravenworks' Blog
  • ahubbard83's Blog
  • celiac<3'sme!'s Blog
  • William Parsons
  • Gluten Free Breeze (formerly Brendygirl) Blog
  • Ivanna44's Blog
  • Daily Life and Compromising
  • Vonnie Mostat
  • Aly'smom's Blog
  • ar8's Blog
  • farid's Blog
  • Sandra Lee's Blog
  • Demertitis hepaformis no Celac
  • Vonnie Mostat, R.N.
  • beetle's Blog
  • Sandra Lee's Blog
  • carlyng4's Blog
  • totalallergyman's Blog
  • Kim
  • Vhips
  • twinsmom's Blog
  • Newbyliz's Blog
  • collgwg's Blog
  • Living in the Gluten Free World
  • lisajs38's Blog
  • Mary07's Blog
  • Treg immune celsl, short chain fatty acids, gut bacteria etc.
  • questions
  • A Blog by Yvonne (Vonnie) Mostat, RN
  • ROBIN
  • covsooze's Blog
  • HeartMagic's Blog
  • electromobileplace's Blog
  • Adventures of a Gluten Free Mom
  • Fiona S
  • bluff wallace's Blog
  • sweetbroadway's Blog
  • happybingf's Blog
  • Carla
  • jaru24's Blog
  • AngelaMH's Blog
  • collgwg's Blog
  • blueangel68's Blog
  • SimplyGF Blog
  • Jim L Christie
  • Debbie65's Blog
  • Alcohol, jaundice, and celiac
  • kmh6leh's Blog
  • Gluten Free Mastery
  • james
  • danandbetty1's Blog
  • Feline's Blog
  • Linda Atkinson
  • Auntie Lur: The Blog of a Young Girl
  • KathyNapoleone's Blog
  • Gluten Free and Specialty Diet Recipes
  • Why are people ignoring Celiac Disease, and not understanding how serious it actually is?
  • miasuziegirl's Blog
  • KikiUSA's Blog
  • Amyy's Blog
  • Pete Dixon
  • abigail's Blog
  • CHA's Blog
  • Eczema or Celiac Mom?'s Blog
  • Thoughts
  • International Conference on Gastroenterology
  • Deedle's Blog
  • krackers' Blog
  • cliniclfortin's Blog
  • Mike Menkes' Blog
  • Juanita's Blog
  • BARB OTTUM
  • holman's Blog
  • It's EVERYWHERE!
  • life's Blog
  • writer ann's Blog
  • Ally7's Blog
  • Gluten Busters: Gluten-Free Product Alerts by Celiac.com
  • K Espinoza
  • klc's Blog
  • Pizza&beer's Blog
  • CDiseaseMom's Blog
  • sidinator's Blog
  • Dr Rodney Ford's Blog
  • How and where is it safe to buy cryptocurrency?
  • lucedith's Blog
  • Random Thoughts
  • Kate
  • twin#1's Blog
  • myadrienne's Blog
  • Nampa-Boise Idaho
  • Ursa Major's Blog
  • bakingbarb's Blog
  • Does Celiac Cause Sensitivites To Rx's?
  • delana6303's Blog
  • psychologygrl25's Blog
  • Alcohol and Celiac Disease
  • How do we get it???
  • cooliactic_BOOM's Blog
  • GREAT GF eating in Toronto
  • Gluten-free Food Recommendations!
  • YAY! READ THIS!!
  • BROW-FREE DIET BLOG
  • carib168's Blog
  • A Healing Kitchen
  • Shawn s
  • AZ Gal's Blog
  • mom1's Blog
  • The Beginning - The Diagnosis
  • PeweeValleyKY's Blog
  • solange's Blog
  • Cate K's Blog
  • Layered Vegetable Baked Pasta (gluten-free Vegetarian Lasagna)
  • Gluten Free Teen by Ava
  • mtdawber's Blog
  • sweeet_pea's Blog
  • DCE's Blog
  • Infertility and Celiac Disease
  • What to do in the Mekong Delta in 1 Day?
  • glutenfreenew's Blog
  • Living in the Garden of Eden
  • toddzgrrl02's Blog
  • redface's Blog
  • Gluten Free High Protein
  • Ari
  • Great Harvest Chattanooga's Blog
  • CeliBelli's Blog
  • Aboluk's Blog
  • redface's Blog
  • Being in Control of Your Gluten-Free Diet on a Cruise Ship
  • jayshunee's Blog
  • lilactorgirl's Blog
  • Yummy or Yucky Gluten-Free Foods
  • Electra's Blog
  • Cocerned husband's Blog
  • lilactorgirl's Blog
  • A Little History - My Celiac Disease Diagnosis
  • How to line my stomach
  • sewfunky's Blog
  • Oscar's Blog
  • Chey's Blog
  • The Fun of Gluten-free Breastfeeding
  • Dawnie's Blog
  • Sneaky gluten free goodness!
  • Chicago cubs shirts- A perfect way of showing love towards the baseball team!
  • Granny Garbonzo's Blog
  • GFzinks09's Blog
  • How do I get the Celiac.com podcast on my mp3 player?
  • quantumsugar's Blog
  • Littlebit's Blog
  • Kimberly's Blog
  • Dayz's Blog
  • Swimming Breadcrumbs and Other Issues
  • Helen Burdass
  • celiacsupportnancy's Blog
  • Life of an Aggie Celiac
  • kyleandjra.jacobson's Blog
  • Hey! I'm Not "Allergic" to Wheat!
  • FoOdFaNaTic's Blog
  • Wendy Cohan, RN's Gluten-Free and Dairy-Free Cooking Classes
  • Lora Derry
  • Dr. Joel Goldman's Blog
  • The Ultimate Irony
  • Lora Derry
  • ACK514's Blog
  • katinagj's Blog
  • What Goes On, Goes In (Gluten in Skin Care Products)
  • What’s new in hydraulic fittings?
  • cannona3's Blog
  • citykatmm's Blog
  • Adventures in Gluten-Free Toddling
  • tahenderson67's Blog
  • The Dinner Party Drama—Two Guidelines to Assure a Pleasant Gluten-Free Experience
  • What’s new in hydraulic fittings?
  • sparkybear's Blog
  • justbikeit77's Blog
  • To "App" or Not to "App": The Use of Gluten Free Product List Computer Applications
  • Onangwatgo
  • Raine's Blog
  • lalla's Blog
  • To die for Cookie Crumb Gluten-Free Pie Crust
  • DeeTee33's Blog
  • http://glutenfreegroove.com/blog/
  • David2055's Blog
  • Gluten-Free at the Fancy Food Show in San Francisco
  • Kup wysokiej jakości paszporty, prawa jazdy, dowody osobiste
  • Janie's Blog
  • Managing Hives & Gluten Allergies
  • Bogaert's Blog
  • Janie's Blog
  • RaeD's Blog
  • Dizzying Disclaimers!
  • Dream Catcher's Blog
  • PinkZebra's Blog
  • Hibachi Food and Hidden Gluten Hazards (How to Celebrate Gluten-Free)
  • jktenner's Blog
  • OhSoTired's Blog
  • PinkZebra's Blog
  • gluten-free Lover's Blog
  • Gluen Free Health Australia
  • Melissamb21's Blog
  • Andy C's Blog
  • halabackgirl9129's Blog
  • Liam Edwards' Blog
  • Celiac Disease in Africa?
  • Suz's Blog
  • Gluten-Free Fast Food
  • Eldene Goosen
  • mis_chiff's Blog
  • gatakat's Blog
  • macocha's Blog
  • Newly Diagnosed Celiacs Needed for Study in Chicago
  • Elaine Anne
  • Poor Baby's Blog
  • the loonie celiac's Blog
  • jenlex's Blog
  • Sex Drive/Testosterone can be Depleted by Certain Foods
  • Sharon
  • samantha79's Blog
  • 21 Months into the Gluten-free Diet
  • WashingtonLady's Blog-a-log
  • James S. Reid's Blog
  • Living with a Gluten-Free Husband
  • Diane King
  • runner girl's Blog
  • kp3972's Blog
  • ellie_lynn's Blog
  • trayne91's Blog
  • Gluten-free Lipstick!
  • Debado
  • Nonna2's Blog
  • Schar Chocolate Hazelnut Bar (Gluten-Free)
  • Diane
  • pnltbox27's Blog
  • Live2BWell's Blog
  • melissajohnson's Blog
  • nvsmom's Blog
  • Diagnosed with Celiac Disease and Still Sick
  • Coming out having gluten intolerance and celiac disease
  • snowcoveredheart's Blog
  • Gluten Free Nurse
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  1. 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. Specifically, 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. 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: J Exp Med. 2012 Dec 17;209(13):2395-408. doi: 10.1084/jem.20102660
  2. Celiac.com 12/22/2016 - The nature of gut intraepithelial lymphocytes (IELs) lacking antigen receptors remains controversial. A team of researchers recently set out to better understand the mechanisms by which innate intraepithelial lymphocytes develop in the intestine and become cancerous in celiac disease patients. The research team included J Ettersperger, N Montcuquet, G Malamut, N Guegan, S Lopez-Lastra, S Gayraud, C Reimann, E Vidal, N Cagnard, P Villarese, I Andre-Schmutz, R Gomes Domingues, C Godinho-Silva, H Veiga-Fernandes, L Lhermitte, V Asnafi, E Macintyre, C Cellier, K Beldjord, JP Di Santo, N Cerf-Bensussan, and B Meresse. They are variously affiliated with the INSERM UMR1163, Laboratory of Intestinal Immunity, Institut Imagine; Laboratory of Human Lymphohematopoiesis; Institut Necker-Enfants-Malades, INSERM UMR1151 and, Biological Hematology, AP-HP Necker-Enfants-Malades; the Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine in Paris, France; AP-HP, Department of Gastroenterology, Hôpital Européen Georges Pompidou, 75015 Paris, France; Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France; Innate Immunity Unit, Institut Pasteur, 75015 Paris, France; INSERM U 668, Paris, France; Paris-Descartes Bioinformatic Platform, 75015 Paris, France; and with the Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa in Lisbon, Portugal. The team was able to show, in humans and in mice, innate intestinal IELs expressing intracellular CD3 (iCD3(+)) differentiate along an Id2 transcription factor (TF)-independent pathway in response to TF NOTCH1, interleukin-15 (IL-15), and Granzyme B signals. In NOTCH1-activated human hematopoietic precursors, IL-15 induced Granzyme B, which cleaved NOTCH1 into a peptide lacking transcriptional activity. As a result, NOTCH1 target genes necessary for T cell differentiation were silenced, and precursors were reprogrammed into innate cells with T cell marks, including intracellular CD3 and T cell rearrangements. In the intraepithelial lymphoma complicating celiac disease, iCD3(+) innate IELs acquired gain-of-function mutations in Janus kinase 1 or Signal transducer and activator of transcription 3, which enhanced their response to IL-15. The research team observed and described gut T cell-like innate IELs, decoded their pathway of change, and showed their malignant transformation in celiac disease. This study offers an exciting glimpse into the hard work being done in the far corners of celiac disease and cancer research. Source: Immunity. 2016 Sep 20;45(3):610-25. doi: 10.1016/j.immuni.2016.07.018. Epub 2016 Sep 6.

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  4. Celiac.com 08/16/2016 - Celiac disease changes the composition and differentiation potential of the duodenal intraepithelial innate lymphocyte compartment, specifically, the composition and function of duodenal intraepithelial T cells. The intestinal tract is also home to four types of CD3-negative intraepithelial lymphocytes (IELs) with largely unknown function: CD56(-)CD127(-); CD56(-)CD127(+); CD56(+)CD127(-) and CD56(+)CD127(+). A team of researchers wanted to gain insight into the potential function of these innate IELs in health and disease. Specifically, they wanted to assess how the composition and differentiation potential of the duodenal intraepithelial innate lymphocyte compartment is altered in celiac disease. The research team included F Schmitz, Y Kooy-Winkelaar, AS Wiekmeijer, MH Brugman, ML Mearin, C Mulder, S Chuva de Sousa Lopes, CL Mummery, FJ Staal, J van Bergen, F Koning. They are variously affiliated with the Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands, the Department of Immunohematology and Blood Transfusion at Leiden University Medical Center in Leiden, The Netherlands, the Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands, the Department of Gastroenterology at the Free University Medical Center, Amsterdam, The Netherlands, and with the Department of Anatomy and Embryology at Leiden University Medical Center in Leiden, The Netherlands. For their study, the team measured the phenotypes, relative abundance and differentiation potential of these innate IEL subsets in duodenal biopsies from controls and patients with celiac disease or patients with refractory celiac disease type II (RCDII). Hierarchical clustering analysis of the expression of 15 natural killer and T cell surface markers showed that innate IELs differed markedly from innate peripheral blood lymphocytes and divided innate IEL subsets into two main branches: a CD127(-) branch expressing high levels of interleukin (IL) 2/15Rβ but no IL-21R, and a CD127(+) branch with the opposite phenotype. While celiac disease was characterized by the contraction of all four innate IEL subsets, a selective expansion of CD56(-)CD127(-) and CD56(-)CD127(+) innate IEL was detected in RCDII. In vitro, in the presence of IL-15, CD56(-)CD127(-) IEL from controls and patients with celiac disease differentiated into functional natural killer and T cells, the latter largely dependent on notch-signaling. This did not occur in patients with RCDII. Furthermore, compared with non-celiac controls, CD56(-)CD127(-) IEL from patients with celiac disease expressed more intracellular CD3ε and CD3γ and gave more pronounced T cell differentiation. RCDII changes the normally diverse and plastic innate IEL compartment, and encourages a loss of differentiation potential. Source: Gut. 2016 Aug;65(8):1269-78. doi: 10.1136/gutjnl-2014-308153.
  5. Celiac.com 07/18/2016 - Researchers still don't have a very good understanding about what triggers non-celiac wheat sensitivity. To get a better idea, a team of researchers recently set out to examine the inflammatory response in the rectal mucosa of patients with well-defined non-celiac wheat sensitivity. Specifically, they wanted to look at type 1 innate lymphoid cells in the rectal mucosa of those patients. The research team included Diana Di Liberto, Pasquale Mansueto, Alberto D'Alcamo, Marianna Lo Pizzo, Elena Lo Presti1, Girolamo Geraci, Francesca Fayer, Giuliana Guggino, Giuseppe Iacono, Francesco Dieli, and Antonio Carroccio. They are variously affiliated with the Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy, the Dipartimento di Biopatologia e Biotecnologie Mediche (DIBIMED), University of Palermo, Palermo, Italy, the Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy, the Surgery Department at the University of Palermo in Palermo, Italy, and with the Pediatric Gastroenterology, ARNAS Di Cristina Hospital, Palermo, Italy 6Internal Medicine, Giovanni Paolo II Hospital, Sciacca (ASP Agrigento), Palermo, Italy. For their study, the team included 22 patients with irritable bowel syndrome (IBS)-like clinical presentation, diagnosed with non-celiac wheat sensitivity by double-blind placebo-controlled challenge. As control subjects, they used eight IBS patients who were not improving on wheat-free diet. Two weeks after each of the subjects consumed 80 grams of wheat daily as part of an oral challenge, the researchers isolated cells from rectal biopsies and thoroughly characterized them using fluorescence-activated cell sorting analysis for intracellular cytokines and surface markers. Analysis of the rectal biopsies of wheat-challenged non-celiac wheat sensitivity patients showed that a significant mucosal CD45+ infiltrate consisted of CD3+ and CD3− lymphocytes, with the latter spontaneously producing more interferon (IFN)-γ than IBS controls. About 30% of IFN-γ-producing CD45+ cells were T-bet+, CD56−, NKP44−, and CD117−, defining them as a type-1 innate lymphoid cells (ILC1). IFN-γ-producing ILC1 cells significantly decreased in 10 patients analyzed 2 weeks after they resumed a wheat-free diet. This study shows that IFN-γ-producing ILC1 cells infiltrate rectal mucosa, promoting the lymphoid cell population, which gives rise to non-celiac wheat sensitivity. Source: Clinical and Translational Gastroenterology, 2016 doi:10.1038/ctg.2016.35
  6. Celiac.com 04/10/2006 - This study looks at innate immune response to gliadin. The innate immune system responds to gliadin inducing zonulin release and increasing intestinal permeability and may be a factor in the onset of celiac disease, but I question if this leads ultimately to the Ag-specific adaptive immune response seen in patients with celiac disease. This innate response fails to explain why one identical twin may have celiac disease and not the other. Both of the twins as well as people not even susceptible to celiac disease would presumably have this same innate response to gliadin. I again urge celiac disease researchers to consider gluten-internalizing bacteria as the necessary trigger for the onset of celiac disease. The presence or absence of such bacteria does indeed offer an explanation as to why one twin gets celiac disease and not the other. Zonulin does not. In the commercial supplement product, Glisodin, the properties of gliadin have, in fact, already been used for the last few years to facilitate the delivery of the antioxidant enzyme superoxide dismutase (SOD) protecting it from digestive acids and getting it through the intestinal mucosa, probably taking advantage of the zonulin effect. Aware of celiac disease, the developer of Glisodin tried to use other peptides as a carrier of SOD, but the only gliadin was effective. Unfortunately, this denies celiacs the benefit of using Glisodin to treat oxidative stress. Abstract of Study: J Immunol. 2006 Feb 15;176(4):2512-21. Gliadin Stimulation of Murine Macrophage Inflammatory Gene Expression and Intestinal Permeability Are MyD88-Dependent: Role of the Innate Immune Response in Celiac Disease. Thomas KE, Sapone A, Fasano A, Vogel SN. Department of Microbiology and Immunology. Recent studies have demonstrated the importance of TLR signaling in intestinal homeostasis. Celiac disease (celiac disease) is an autoimmune enteropathy triggered in susceptible individuals by the ingestion of gliadin-containing grains. In this study, we sought to test the hypothesis that gliadin initiates this response by stimulating the innate immune response to increase intestinal permeability and by up-regulating macrophage proinflammatory gene expression and cytokine production. To this end, intestinal permeability and the release of zonulin (an endogenous mediator of gut permeability) in vitro, as well as proinflammatory gene expression and cytokine release by primary murine macrophage cultures, were measured. Gliadin and its peptide derivatives, 33-mer and p31-43, were found to be potent inducers of both a zonulin-dependent increase in intestinal permeability and macrophage proinflammatory gene expression and cytokine secretion. Gliadin-induced zonulin release, increased intestinal permeability, and cytokine production were dependent on myeloid differentiation factor 88 (MyD88), a key adapter molecule in the TLR/IL-1R signaling pathways, but were neither TLR2- nor TLR4-dependent. Our data support the following model for the innate immune response to gliadin in the initiation of celiac disease. Gliadin interaction with the intestinal epithelium increases intestinal permeability through the MyD88-dependent release of zonulin that, in turn, enables paracellular translocation of gliadin and its subsequent interaction with macrophages within the intestinal submucosa. There, the interaction of gliadin with macrophages elicits a MyD88-dependent proinflammatory cytokine milieu that facilitates the interaction of T cells with APCs, leading ultimately to the Ag-specific adaptive immune response seen in patients with celiac disease.
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