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Review

Molecular mechanisms of the adaptive, innate and regulatory immune responses in the intestinal mucosa of celiac disease patients

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Pages 681-700 | Published online: 09 Jan 2014

References

  • Shewry PR, Halford NG. Cereal seed storage proteins: structures, properties and role in grain utilization. J. Exp. Bot. 53, 947–958 (2002).
  • Wieser H. Relation between gliadin structure and coeliac toxicity. Acta Paediatr. Suppl. 412, 3–9 (1996).
  • Eaton SB, Eaton SB III,Konner MJ. Paleolithic nutrition revisited: a twelve-year retrospective on its nature and implications. Eur. J. Clin. Nutr. 51, 207–216 (1997).
  • Rewers M. Epidemiology of celiac disease: what are the prevalence, incidence, and progression of celiac disease? Gastroenterology 128, S47–S51 (2005).
  • Dube C, Rostom A, Sy R et al. The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review. Gastroenterology 128, S57–S67 (2005).
  • Fasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology 120, 636–651 (2001).
  • Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology 102, 330–354 (1992).
  • Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch. Dis. Child. 65, 909–911 (1990).
  • Rostom A, Dube C, Cranney A et al. The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology 128, S38–S46 (2005).
  • Vader LW, Stepniak DT, Bunnik EM et al. Characterization of cereal toxicity for celiac disease patients based on protein homology in grains. Gastroenterology 125, 1105–1113 (2003).
  • Shan L, Molberg O, Parrot I et al. Structural basis for gluten intolerance in celiac sprue. Science 297, 2275–2279 (2002).
  • Greco L, Romino R, Coto I et al. The first large population based twin study of coeliac disease. Gut 50, 624–628 (2002).
  • Sollid LM. Coeliac disease: dissecting a complex inflammatory disorder. Nature Rev. Immunol. 2, 647–655 (2002).
  • Babron MC, Nilsson S, Adamovic S et al. Meta and pooled analysis of European coeliac disease data. Eur. J. Hum. Genet. 11, 828–834 (2003).
  • Van Belzen MJ, Meijer JW, Sandkuijl LA et al. A major non-HLA locus in celiac disease maps to chromosome 19. Gastroenterology 125, 1032–1041 (2003).
  • Greco L, Babron MC, Corazza GR et al. Existence of a genetic risk factor on chromosome 5q in Italian coeliac disease families. Ann. Hum. Genet. 65, 35–41 (2001).
  • Greco L, Corazza G, Babron MC et al. Genome search in celiac disease. Am. J. Hum. Genet. 62, 669–675 (1998).
  • Percopo S, Babron MC, Whalen M et al. Saturation of the 5q31–q33 candidate region for coeliac disease. Ann. Hum. Genet. 67, 265–268 (2003).
  • Rioux JD, Karinen H, Kocher K et al. Genomewide search and association studies in a Finnish celiac disease population: Identification of a novel locus and replication of the HLA and CTLA4 loci. Am. J. Hum. Genet. 130, 345–350 (2004).
  • Bevan S, Popat S, Braegger CP et al. Contribution of the MHC region to the familial risk of coeliac disease. J. Med. Genet. 36, 687–690 (1999).
  • Hunt KA, McGovern DP, Kumar PJ et al. A common CTLA4 haplotype associated with coeliac disease. Eur. J. Hum. Genet. 13, 440–444 (2005).
  • Naluai AT, Nilsson S, Samuelsson L et al. The CTLA4/CD28 gene region on chromosome 2q33 confers susceptibility to celiac disease in a way possibly distinct from that of Type 1 diabetes and other chronic inflammatory disorders. Tissue Antigens 56, 350–355 (2000).
  • Djilali-Saiah I, Schmitz J, Harfouch-Hammoud E et al. CTLA-4 gene polymorphism is associated with predisposition to coeliac disease. Gut 43, 187–189 (1998).
  • Clot F, Fulchignoni-Lataud MC, Renoux C et al. Linkage and association study of the CTLA-4 region in coeliac disease for Italian and Tunisian populations. Tissue Antigens 54, 527–530 (1999).
  • Popat S, Hearle N, Hogberg L et al. Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease. Ann. Hum. Genet. 66, 125–137 (2002).
  • Popat S, Hearle N, Wixey J et al. Analysis of the CTLA4 gene in Swedish coeliac disease patients. Scand. J. Gastroenterol. 37, 28–31 (2002).
  • Holopainen P, Naluai AT, Moodie S et al. Candidate gene region 2q33 in European families with coeliac disease. Tissue Antigens 63, 212–222 (2004).
  • King AL, Moodie SJ, Fraser JS et al. CTLA-4/CD28 gene region is associated with genetic susceptibility to coeliac disease in UK families. J. Med. Genet. 39, 51–54 (2002).
  • Martin-Pagola A, Perez de Nanclares G, Vitoria JC et al. No association of CTLA4 gene with celiac disease in the Basque population. J. Pediatr. Gastroenterol. Nutr. 37, 142–145 (2003).
  • van Belzen MJ, Mulder CJ, Zhernakova A et al. CTLA4 +49 A/G and CT60 polymorphisms in Dutch coeliac disease patients. Eur. J. Hum. Genet. 12, 782–785 (2004).
  • Amundsen SS, Naluai AT, Ascher H et al. Genetic analysis of the CD28/CTLA4/ICOS (CELIAC3) region in coeliac disease. Tissue Antigens 64, 593–599 (2004).
  • Haimila K, Smedberg T, Mustalahti K et al. Genetic association of coeliac disease susceptibility to polymorphisms in the ICOS gene on chromosome 2q33. Genes Immun. 5, 85–92 (2004).
  • Mora B, Bonamico M, Indovina P et al. CTLA-4 +49 A/G dimorphism in Italian patients with celiac disease. Hum. Immunol. 64, 297–301 (2003).
  • Holopainen P, Arvas M, Sistonen P et al. CD28/CTLA4 gene region on chromosome 2q33 confers genetic susceptibility to celiac disease. A linkage and family-based association study. Tissue Antigens 53, 470–475 (1999).
  • King AL, Moodie SJ, Fraser JS et al. Coeliac disease: investigation of proposed causal variants in the CTLA4 gene region. Eur. J. Immunogenet. 30, 427–432 (2003).
  • Diosdado B, Wapenaar MC, Franke L et al. A microarray screen for novel candidate genes in coeliac disease pathogenesis. Gut 53, 944–951 (2004).
  • Juuti-Uusitalo K, Maki M, Kaukinen K et al. cDNA microarray analysis of gene expression in coeliac disease jejunal biopsy samples. J. Autoimmun. 22, 249–265 (2004).
  • Sollid LM. Molecular basis of celiac disease. Ann. Rev. Immunol. 18, 53–81 (2000).
  • Meresse B, Chen Z, Ciszewski C et al. Co-ordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 21, 357–366 (2004).
  • Hue S, Mention JJ, Monteiro RC et al. A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity 21, 367–377 (2004).
  • Maiuri L, Ciacci C, Ricciardelli I et al. Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease. Lancet 362, 30–37 (2003).
  • MacDonald TT. The mucosal immune system. Parasite Immunol. 25, 235–246 (2003).
  • Mowat AM. Anatomical basis of tolerance and immunity to intestinal antigens. Nature Rev. Immunol. 3, 331–341 (2003).
  • Spahn TW, Fontana A, Faria AM et al. Induction of oral tolerance to cellular immune responses in the absence of Peyer’s patches. Eur. J. Immunol. 31, 1278–1287 (2001).
  • Chehade M, Mayer L. Oral tolerance and its relation to food hypersensitivities. J. Allergy Clin. Immunol. 115, 3–12 (2005).
  • Strobel S, Mowat AM. Immune responses to dietary antigens: oral tolerance. Immunol. Today. 19, 173–181 (1998).
  • Mayer L, Shao L. Therapeutic potential of oral tolerance. Nature Rev. Immunol. 4, 407–419 (2004).
  • Chen Y, Inobe J, Marks R et al. Peripheral deletion of antigen-reactive T cells in oral tolerance. Nature 376, 177–180 (1995).
  • Appleman LJ, Boussiotis VA. T cell anergy and costimulation. Immunol. Rev. 192, 161–180 (2003).
  • Weiner HL. Induction and mechanism of action of transforming growth factor-β-secreting Th3 regulatory cells. Immunol. Rev. 182, 207–214 (2001).
  • Groux H, O’Garra A, Bigler M et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737–742 (1997).
  • Kim PH, Kagnoff MF. Transforming growth factor-β 1 is a costimulator for IgA production. J. Immunol. 144, 3411–3416 (1990).
  • Zhang X, Izikson L, Liu L, Weiner HL. Activation of CD25+CD4+ regulatory T cells by oral antigen administration. J. Immunol. 167, 4245–4253 (2001).
  • Ostroukhova M, Seguin-Devaux C, Oriss TB et al. Tolerance induced by inhaled antigen involves CD4(+) T cells expressing membrane-bound TGF-β and FOXP3. J. Clin. Invest. 114, 28–38 (2004).
  • Bennett CL, Christie J, Ramsdell F et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nature Genet. 27, 20–21 (2001).
  • Lionetti P, Pazzaglia A, Moriondo M et al. Differing patterns of transforming growth factor-β expression in normal intestinal mucosa and in active celiac disease. J. Pediatr. Gastroenterol. Nutr. 29, 308–313 (1999).
  • Hansson T, Ulfgren AK, Lindroos E et al. Transforming growth factor-β (TGF-β) and tissue transglutaminase expression in the small intestine in children with coeliac disease. Scand. J. Immunol. 56, 530–537 (2002).
  • Perez-Machado MA, Ashwood P, Thomson MA et al. Reduced transforming growth factor-β1-producing T cells in the duodenal mucosa of children with food allergy. Eur. J. Immunol. 33, 2307–2315 (2003).
  • Lahat N, Shapiro S, Karban A et al. Cytokine profile in coeliac disease. Scand. J. Immunol. 49, 441–446 (1999).
  • Forsberg G, Hernell O, Melgar S et al. Paradoxical coexpression of pro-inflammatory and downregulatory cytokines in intestinal T cells in childhood celiac disease. Gastroenterology 123, 667–678 (2002).
  • Nilsen EM, Jahnsen FL, Lundin KE et al. Gluten induces an intestinal cytokine response strongly dominated by interferon γ in patients with celiac disease. Gastroenterology 115, 551–563 (1998).
  • Woolley N, Mustalahti K, Maki M, Partanen J. Cytokine gene polymorphisms and genetic association with coeliac disease in the Finnish population. Scand. J. Immunol. 61, 51–56 (2005).
  • Beckett CG, Dell’Olio D, Kontakou M et al. Analysis of interleukin-4 and interleukin-10 and their association with the lymphocytic infiltrate in the small intestine of patients with coeliac disease. Gut 39, 818–823 (1996).
  • Cataldo F, Lio D, Marino V et al. Cytokine genotyping (TNF and IL-10) in patients with celiac disease and selective IgA deficiency. Am. J. Gastroenterol. 98, 850–856 (2003).
  • Hahn-Zoric M, Hytonen AM, Hanson LA, Nilsson LA, Padyukov L. Association of -1087 IL10 and -308 TNF A gene polymorphisms with serological markers of coeliac disease. J. Clin. Immunol. 23, 291–296 (2003).
  • Di Sabatino A, Ciccocioppo R, Carsetti R, Rosado MM, Cupelli F, Corazza GR. Defect of mucosal CD4+ CD25+ regulatory T-cells in coeliac disease. 11th International Symposium on Coeliac Disease, Belfast, UK (2004) (Abstract).
  • Vaidya B, Pearce S. The emerging role of the CTLA-4 gene in autoimmune endocrinopathies. Eur. J. Endocrinol. 150, 619–626 (2004).
  • Ueda H, Howson JM, Esposito L et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423, 506–511 (2003).
  • Charles A Janeway PT, Mark Walport, Mark Shlomchik. In: Immunobiology: The Immune System in Health and Disease. Garland Publishing, NY, USA (2001).
  • Schuppan D. Current concepts of celiac disease pathogenesis. Gastroenterology 119, 234–242 (2000).
  • Vader W, Stepniak D, Kooy Y et al. The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses. Proc. Natl Acad. Sci. USA 100, 12390–12395 (2003).
  • Vader W, Kooy Y, Van Veelen P et al. The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides. Gastroenterology 122, 1729–1737 (2002).
  • Monteleone I, Monteleone G, Del Vecchio Blanco G et al. Regulation of the T helper cell Type 1 transcription factor T-bet in coeliac disease mucosa. Gut 53, 1090–5 (2004).
  • Salvati VM, MacDonald TT, Bajaj-Elliott M et al. Interleukin-18 and associated markers of T helper cell Type 1 activity in coeliac disease. Gut 50, 186–190 (2002).
  • Monteleone G, Pender SL, Alstead E et al. Role of interferon α in promoting T helper cell Type 1 responses in the small intestine in coeliac disease. Gut 48, 425–429 (2001).
  • Parrello T, Monteleone G, Cucchiara S et al. Upregulation of the IL-12 receptor β2 chain in Crohn’s disease. J. Immunol. 165, 7234–7239 (2000).
  • Seegers D, Borm ME, van Belzen MJ et al. IL12B and IRF1 gene polymorphisms and susceptibility to celiac disease. Eur. J. Immunogenet. 30, 421–425 (2003).
  • Louka AS, Torinsson Naluai A, D’Alfonso S et al. The IL12B gene does not confer susceptibility to coeliac disease. Tissue Antigens 59, 70–72 (2002).
  • Przemioslo RT, Kontakou M, Nobili V, Ciclitira PJ. Raised pro-inflammatory cytokines interleukin-6 and tumour necrosis factor α in coeliac disease mucosa detected by immunohistochemistry. Gut 35, 1398–1403 (1994).
  • Westerholm-Ormio M, Garioch J, Ketola I, Savilahti E. Inflammatory cytokines in small intestinal mucosa of patients with potential coeliac disease. Clin. Exp. Immunol. 128, 94–101 (2002).
  • Kontakou M, Przemioslo RT, Sturgess RP, Limb AG, Ciclitira PJ. Expression of tumour necrosis factor-α, interleukin-6, and interleukin-2 mRNA in the jejunum of patients with coeliac disease. Scand. J. Gastroenterol. 30, 456–463 (1995).
  • Kontakou M, Przemioslo RT, Sturgess RP et al. Cytokine mRNA expression in the mucosa of treated coeliac patients after wheat peptide challenge. Gut 37, 52–57 (1995).
  • Polvi A, Maki M, Collin P, Partanen J. TNF microsatellite alleles a2 and b3 are not primarily associated with celiac disease in the Finnish population. Tissue Antigens 51, 553–555 (1998).
  • de la Concha EG, Fernandez-Arquero M, Vigil P et al. Celiac disease and TNF promoter polymorphisms. Hum. Immunol. 61, 513–517 (2000).
  • Garrote JA, Arranz E, Telleria JJ et al. TNF α and LT α gene polymorphisms as additional markers of celiac disease susceptibility in a DQ2-positive population. Immunogenetics 54, 551–555 (2002).
  • Louka AS, Lie BA, Talseth B et al. Coeliac disease patients carry conserved HLA-DR3-DQ2 haplotypes revealed by association of TNF alleles. Immunogenetics 55, 339–343 (2003).
  • Louka AS, Moodie SJ, Karell K et al. A collaborative European search for non-DQA1*05-DQB1*02 celiac disease loci on HLA-DR3 haplotypes: analysis of transmission from homozygous parents. Hum. Immunol. 64, 350–358 (2003).
  • Salvati VM, Mazzarella G, Gianfrani C et al. Recombinant human interleukin-10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa. Gut 54, 46–53 (2005).
  • Wapenaar MC, van Belzen MJ, Fransen JH et al. The interferon γ gene in celiac disease: augmented expression correlates with tissue damage but no evidence for genetic susceptibility. J. Autoimmun. 23, 183–190 (2004).
  • Breese EJ, Kumar P, Farthing MJ, MacDonald TT. Interleukin-2 and interferon-γ producing cells in the lamina propria in celiac disease. Dig. Dis. Sci. 39, 2243 (1994).
  • Veres G, Westerholm-Ormio M, Kokkonen J, Arato A, Savilahti E. Cytokines and adhesion molecules in duodenal mucosa of children with delayed-type food allergy. J. Pediatr. Gastroenterol. Nutr. 37, 27–34 (2003).
  • Kontakou M, Sturgess RP, Przemioslo RT et al. Detection of interferon γ mRNA in the mucosa of patients with coeliac disease by in situ hybridisation. Gut 35, 1037–1041 (1994).
  • al-Dawoud A, Nakshabendi I, Foulis A, Mowat AM. Immunohistochemical analysis of mucosal γ-interferon production in coeliac disease. Gut 33, 1482–1486 (1992).
  • Przemioslo RT, Lundin KE, Sollid LM, Nelufer J, Ciclitira PJ. Histological changes in small bowel mucosa induced by gliadin sensitive T lymphocytes can be blocked by anti-interferon γ antibody. Gut 36, 874–879 (1995).
  • Shuai K, Liu B. Regulation of JAK-STAT signalling in the immune system. Nature Rev. Immunol. 3, 900–911 (2003).
  • Mazzarella G, MacDonald TT, Salvati VM et al. Constitutive activation of the signal transducer and activator of transcription pathway in celiac disease lesions. Am. J. Pathol. 162, 1845–1855 (2003).
  • Salvati VM, MacDonald TT, del Vecchio Blanco G et al. Enhanced expression of interferon regulatory factor-1 in the mucosa of children with celiac disease. Pediatr. Res. 54, 312–318 (2003).
  • Jones SC, Trejdosiewicz LK, Banks RE et al. Expression of interleukin-6 by intestinal enterocytes. J. Clin. Pathol. 46, 1097–1100 (1993).
  • Ryan AW, Thornton JM, Brophy K et al. Chromosome 5q candidate genes in coeliac disease: genetic variation at IL4, IL5, IL9, IL13, IL17B and NR3C1. Tissue Antigens 65, 150–155 (2005).
  • Desreumaux P, Delaporte E, Colombel JF et al. Similar IL-5, IL-3, and GM-CSF syntheses by eosinophils in the jejunal mucosa of patients with celiac disease and dermatitis herpetiformis. Clin. Immunol. Immunopathol. 88, 14–21 (1998).
  • Desreumaux P, Janin A, Colombel JF et al. Interleukin-5 messenger RNA expression by eosinophils in the intestinal mucosa of patients with coeliac disease. J. Exp. Med. 175, 293–296 (1992).
  • Sansonetti PJ. War and peace at mucosal surfaces. Nature Rev. Immunol. 4, 953–964 (2004).
  • Maiuri L, Auricchio S, Coletta S et al. Blockage of T-cell costimulation inhibits T-cell action in celiac disease. Gastroenterology 115, 564–572 (1998).
  • Maiuri L, Picarelli A, Boirivant M et al. Definition of the initial immunologic modifications upon in vitro gliadin challenge in the small intestine of celiac patients. Gastroenterology 110, 1368–1378 (1996).
  • Picarelli A, Maiuri L, Mazzilli MC et al. Gluten-sensitive disease with mild enteropathy. Gastroenterology 111, 608–616 (1996).
  • Mention JJ, Ben Ahmed M, Begue B et al. Interleukin-15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease. Gastroenterology 125, 730–745 (2003).
  • Martin-Pagola A, Ortiz L, Perez de Nanclares G et al. Analysis of the expression of MICA in small intestinal mucosa of patients with celiac disease. J. Clin. Immunol. 23, 498–503 (2003).
  • Fernandez L, Fernandez-Arquero M, Gual L et al. Triplet repeat polymorphism in the transmembrane region of the MICA gene in celiac disease. Tissue Antigens 59, 219–222 (2002).
  • Rueda B, Pascual M, Lopez-Nevot MA et al. Association of MICA-A5.1 allele with susceptibility to celiac disease in a family study. Am. J. Gastroenterol. 98, 359–362 (2003).
  • Lopez-Vazquez A, Rodrigo L, Fuentes D et al. MICA-A5.1 allele is associated with atypical forms of celiac disease in HLA-DQ2-negative patients. Immunogenetics 53, 989–991 (2002).
  • Lopez-Vazquez A, Rodrigo L, Fuentes D et al. MHC class I chain related gene A (MICA) modulates the development of coeliac disease in patients with the high risk heterodimer DQA1*0501/DQB1*0201. Gut 50, 336–340 (2002).
  • Diosdado B van Oort E, Wijmenga C. ‘Celionomics’: towards understanding the molecular pathology of celiac disease. Clin. Chem. Lab. Med.(2005) (In Press).
  • Ciccocioppo R, Di Sabatino A, Parroni R et al. Increased enterocyte apoptosis and Fas–Fas ligand system in celiac disease. Am. J. Clin. Pathol. 115, 494–503 (2001).
  • Maiuri L, Ciacci C, Raia V et al. FAS engagement drives apoptosis of enterocytes of coeliac patients. Gut 48, 418–424 (2001).
  • Di Sabatino A, Ciccocioppo R, D’Alo S et al. Intraepithelial and lamina propria lymphocytes show distinct patterns of apoptosis whereas both populations are active in Fas based cytotoxicity in coeliac disease. Gut 49, 380–386 (2001).
  • Ehrmann J Jr., Kolek A, Kod’ousek R et al. Immunohistochemical study of the apoptotic mechanisms in the intestinal mucosa during children’s coeliac disease. Virchows Arch. A. 442, 453–461 (2003).
  • Giovannini C, Matarrese P, Scazzocchio B et al. Wheat gliadin induces apoptosis of intestinal cells via an autocrine mechanism involving Fas-Fas ligand pathway. FEBS Lett. 540, 117–124 (2003).
  • Daum S, Bauer U, Foss HD et al. Increased expression of mRNA for matrix metalloproteinases-1 and -3 and tissue inhibitor of metalloproteinases-1 in intestinal biopsy specimens from patients with coeliac disease. Gut 44, 17–25 (1999).
  • Daum S, Bauer U, Foss HD et al. Expression of matrix metalloprotease-1 and collagen I mRNA in biopsies from patients with celiac disease. Ann. NY Acad. Sci. 859, 254–257 (1998).
  • Salmela MT, MacDonald TT, Black D et al. Upregulation of matrix metalloproteinases in a model of T cell mediated tissue injury in the gut: analysis by gene array and in situ hybridisation. Gut 51, 540–547 (2002).
  • Pender SL, Tickle SP, Docherty AJ et al. A major role for matrix metalloproteinases in T cell injury in the gut J. Immunol. 158, 1582–1590 (1997).
  • Rivabene R, Mancini E, De Vincenzi M. In vitro cytotoxic effect of wheat gliadin-derived peptides on the Caco-2 intestinal cell line is associated with intracellular oxidative imbalance: implications for coeliac disease. Biochim. Biophys. Acta. 1453, 152–160 (1999).
  • Elli L, Dolfini E, Bardella MT. Gliadin cytotoxicity and in vitro cell cultures. Toxicol. Lett. 146, 1–8 (2003).
  • Stahlberg MR, Hietanen E, Maki M. Mucosal biotransformation rates in the small intestine of children. Gut 29, 1058–1063 (1988).
  • Odetti P, Valentini S, Aragno I et al. Oxidative stress in subjects affected by celiac disease. Free Radic. Res. 29, 17–24 (1998).
  • Lavy A, Ben Amotz A, Aviram M. Increased susceptibility to undergo lipid peroxidation of chylomicrons and low-density lipoprotein in celiac disease. Ann. Nutr. Metabol. 37, 68–74 (1993).
  • Maiuri MC, De Stefano D, Mele G et al. Gliadin increases iNOS gene expression in interferon-γ-stimulated RAW 264.7 cells through a mechanism involving NF-κB. Naunyn Schmiedebergs Arch. Pharmacol. 368, 63–71 (2003).
  • Bach SP, Renehan AG, Potten CS. Stem cells: the intestinal stem cell as a paradigm. Carcinogenesis 21, 469–476 (2000).
  • Salvati VM, Bajaj-Elliott M, Poulsom R et al. Keratinocyte growth factor and coeliac disease. Gut 49, 176–181 (2001).
  • Senger S, Luongo D, Maurano F et al. Intranasal administration of a recombinant α-gliadin downregulates the immune response to wheat gliadin in DQ8 transgenic mice. Immunol. Lett. 88, 127–134 (2003).
  • Choi K, Siegel M, Piper JL et al. Chemistry and biology of dihydroisoxazole derivatives: selective inhibitors of human transglutaminase 2. Chem. Biol. 12, 469–475 (2005).
  • De Laurenzi V, Melino G. Gene disruption of tissue transglutaminase. Mol. Cell Biol. 21, 148–155 (2001).
  • Nanda N, Iismaa SE, Owens WA et al. Targeted inactivation of Gh/tissue transglutaminase II. J. Biol. Chem. 276, 20673–20678 (2001).
  • Choy EH, Scott DL, Kingsley GH et al. Control of rheumatoid arthritis by oral tolerance. Arthritis Rheum. 44, 1993–1997 (2001).
  • Thompson DJ, Barron KS, Whitcup SM, Robinson MR. The safety and efficacy of chicken Type II collagen on uveitis associated with juvenile rheumatoid arthritis. Ocul. Immunol. Inflamm. 10, 83–91 (2002).

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