Skip to main content
    • Aa
    • Aa

Dietary strategies of immunomodulation in infants at risk for celiac disease

  • Esther Nova (a1), Tamara Pozo (a1), Yolanda Sanz (a2) and Ascensión Marcos (a1)

Celiac disease is an inflammatory disorder of the small intestine, triggered by the ingestion of gluten proteins contained in wheat, barley or rye, in genetically susceptible individuals. This disorder is considered to be mainly mediated by cellular immunity and restricted to the human leucocyte antigen-DQ presentation of gluten-derived toxic peptides to T-cells. Moreover, the involvement of innate immunity has been recently demonstrated to be necessary also for the development of intestinal tissue damage. Genetic susceptibility accounts for an uncertain proportion of the disease risk and gluten introduction works as the precipitating factor. However, currently, the research interest is also focused on environmental factors and gene–environment interactions, especially during the first months of life, which might help explain the onset of the disease. Infectious and dietary factors that could modulate the immune response orientating it either towards tolerance or intolerance/autoimmunity are the focus of primary attention. A significant number of studies have looked into the protective effect of breast-feeding against the disease. It is generally accepted that breast-feeding during the introduction of dietary gluten and increasing the duration of breast-feeding are associated with reduced risk of developing celiac disease. However, it is still not fully established whether breast-feeding truly protects with permanent tolerance acquisition or only reduces the symptoms and delays the diagnosis. Moreover, the timing and dose of gluten introduction also seem to be relevant and long-term prospective cohort studies are being carried out in order to elucidate its role in celiac disease development.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Dietary strategies of immunomodulation in infants at risk for celiac disease
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Dietary strategies of immunomodulation in infants at risk for celiac disease
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Dietary strategies of immunomodulation in infants at risk for celiac disease
      Available formats
Corresponding author
*Corresponding author: Esther Nova, fax +34 915493627, email
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1. C Gianfrani , S Auricchio & R Troncone (2005) Adaptive and innate immune responses in celiac disease. Immunol Lett 99, 141145.

2. B Meresse , J Ripoche , M Heyman (2009) Celiac disease: from oral tolerance to intestinal inflammation, autoimmunity and lymphomagenesis. Mucosal Immunol 2, 8–23.

3. S Guandalini & M Setty (2008) Celiac disease. Curr Opin Gastroenterol 24, 707712.

4. DA Van Heel , K Hunt , L Greco (2005) Genetics in celiac disease. Best Pract Res Clin Gastroenterol 19, 323339.

5. O Molberg , SN Mcadam , R Körner (1998) Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med 4, 713717.

7. M Ráki , S Tollefsen , Ø Molberg (2006) A unique dendritic cell subset accumulates in the celiac lesion and efficiently activates gluten-reactive T cells. Gastroenterology 131, 428438.

8. AL de Kauwe , Z Chen , RP Anderson (2009) Resistance to celiac disease in humanized HLA-DR3-DQ2-transgenic mice expressing specific anti-gliadin CD4+ T cells. J Immunol 182, 74407450.

9. KE Black , JA Murray & CS David (2002) HLA-DQ determines the response to exogenous wheat proteins: a model of gluten sensitivity in transgenic knockout mice. J Immunol 169, 55955600.

10. R D'Arienzo , F Maurano , D Luongo (2008) Adjuvant effect of Lactobacillus casei in a mouse model of gluten sensitivity. Immunol Lett 119, 7883.

11. T Kutlu , N Brousse , C Rambaud (1993) Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet. Gut 34, 208214.

12. G Bhagat , AJ Naiyer , JG Shah (2008) Small intestinal CD8+TCRgammadelta+NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease. J Clin Invest 118, 281293.

13. B Meresse , Z Chen , C Ciszewski (2004) Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 21, 357366.

14. S Hüe , JJ Mention , RC Monteiro (2004) A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity 21, 367377.

15. L Maiuri , C Ciacci , I Ricciardelli (2003) Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease. Lancet 362, 3037.

16. A Di Sabatino , R Ciccocioppo , F Cupelli (2006) Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease. Gut 55, 469477.

17. G Monteleone , SL Pender , E Alstead (2001) Role of interferon alpha in promoting T helper cell type 1 responses in the small intestine in coeliac disease. Gut 48, 425429.

18. LC Stene , MC Honeyman , EJ Hoffenberg (2006) Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol 101, 23332340.

19. L Plot & H Amital (2009) Infectious associations of Celiac disease. Autoimmun Rev 8, 316319.

20. G Zanoni , R Navone , C Lunardi . (2006) In celiac disease, a subset of autoantibodies against transglutaminase binds toll-like receptor 4 and induces activation of monocytes. PLoS Med 3, e358.

22. B Szebeni , G Veres , A Dezsofi (2007) Increased mucosal expression of Toll-like receptor (TLR)2 and TLR4 in coeliac disease. J Pediatr Gastroenterol Nutr 45, 187193.

23. AK Akobeng , AV Ramanan , I Buchan (2006) Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies. Arch Dis Child 91, 3943.

25. A Ivarsson , LA Persson , L Nyström . (2000) Epidemic of coeliac disease in Swedish children. Acta Paediatr 89, 165171.

26. A Myléus , A Ivarsson , C Webb (2009) Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic. J Pediatr Gastroenterol Nutr 49, 170176.

28. R Troncone , A Ivarsson , H Szajewska (2008) Members of European Multistakeholder Platform on CD (CDEUSSA) (2008) Review article: future research on coeliac disease - a position report from the European multistakeholder platform on coeliac disease (CDEUSSA). Aliment Pharmacol Ther 27, 10301043.

29. JM Norris , K Barriga , EJ Hoffenberg (2005) Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. JAMA 293, 23432351.

30. KM Lammers , R Lu , J Brownley (2008) Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology 135, 194204.

31. C Agostoni , T Decsi , M Fewtrell ESPGHAN Committee on Nutrition (2008) Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 46, 99–110.

32. C Agostoni , C Braegger , T Decsi ESPGHAN Committee on Nutrition (2009) Breast-feeding: A Commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 49, 112125.

33. AM Mowat , AM Faria & HL Weiner (2005) Oral tolerance: basic mechanisms and clinical implications. In Mucosal immunology, 3rd ed., pp. 487538 [ J Mestecky , J Bienenstock and ME Lamm , editors]. San Diego, CA: Academic Press.

34. TT Macdonald & G Monteleone (2005) Immunity, inflammation, and allergy in the gut. Science 307, 19201925.

35. AM Mowat , LA Parker , H Beacon-Sharp (2004) Oral tolerance: overview and historical perspectives. Ann NY Acad Sci 1029, 18.

36. N Cools , P Ponsaerts , VF Van Tendeloo (2007) Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells. J Leukoc Biol 82, 13651374.

37. P Guermonprez , J Valladeau , L Zitvogel (2002) Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 20, 621.

38. S Strobel & AM Mowat (2006) Oral tolerance and allergic responses to food proteins. Curr Opin Allergy Clin Immunol 6, 207213.

39. JL Lowrey , ND Savage , D Palliser (1998) Induction of tolerance via the respiratory mucosa. Int Arch Allergy Immunol 116, 93–102.

40. S Senger , D Luongo , F Maurano (2003) Intranasal administration of a recombinant alpha-gliadin down-regulates the immune response to wheat gliadin in DQ8 transgenic mice. Immunol Lett 88, 127134.

41. A Fasano , M Araya , S Bhatnagar (2008) Celiac Disease Working Group, FISPGHAN. Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition consensus report on celiac disease. J Pediatr Gastroenterol Nutr 47, 214219.

43. M Brenner , T Laragione , NC Yarlett (2007) Genetic regulation of T regulatory, CD4, and CD8 cell numbers by the arthritis severity loci Cia5a, Cia5d, and the MHC/Cia1 in the rat. Mol Med 13, 277287.

44. B Bisikirska , J Colgan , J Luban (2005) TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs. J Clin Invest 115, 29042913.

45. DA Van Heel , L Franke , KA Hunt (2007) A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nat Genet 39, 827829.

46. TO Kerttula , P Collin , A Polvi (1996) Distinct immunologic features of Finnish Sjögren's syndrome patients with HLA alleles DRB1*0301, DQA1*0501, and QB1*0201. Alterations in circulating T cell receptor gamma/delta subsets. Arthritis Rheum 39, 17331739.

48. I Nadal , E Donat , C Ribes-Koninckx (2007) Imbalance in the composition of the duodenal microbiota of children with coeliac disease. J Med Microbiol 56(Pt 12), 16691674.

49. R Menningen & M Bruewer (2009) Effect of probiotics on intestinal barrier function. Ann NY Acad Sci 1165, 183189.

50. M Rossi , F Maurano & D Luongo (2005) Immunomodulatory strategies for celiac disease. Int Rev Immunol 24, 479499.

51. C Gianfrani , RA Siciliano , AM Facchiano (2007) Transamidation of wheat flour inhibits the response to gliadin of intestinal T cells in celiac disease. Gastroenterology 133, 780789.

52. J Xia , E Bergseng , B Fleckenstein (2007) Cyclic and dimeric gluten peptide analogues inhibiting DQ2-mediated antigen presentation in celiac disease. Bioorg Med Chem 15, 65656573.

53. JS Fraser , W Engel , HJ Ellis (2003) Coeliac disease: in vivo toxicity of the putative immunodominant epitope. Gut 52, 16981702.

54. D Branski , A Fasano & R Troncone (2006) Latest developments in the pathogenesis and treatment of celiac disease. J Pediatr 149, 295300.

55. M Silano , O Vincentini , A Iapello (2008) Antagonist peptides of the gliadin T cell stimulatory sequences: a therapeutic strategy for celiac disease. J Clin Gastroenterol 42, Suppl 3, Pt 2, S191S192.

56. VV Kapoerchan , M Wiesner , M Overhand (2008) Design of azidoproline containing gluten peptides to suppress CD4+ T cell responses associated with celiac disease. Bioorg Med Chem 16, 20532062.

57. D Stepniak , L Spaenij-Dekking , C Mitea (2006) Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease. Am J Physiol Gastrointest Liver Physiol 291, G621G629.

58. J Ehren , S Govindarajan , B Morón (2008) Protein engineering of improved prolyl endopeptidases for celiac sprue therapy. Protein Eng Des Sel 21, 699707.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Proceedings of the Nutrition Society
  • ISSN: 0029-6651
  • EISSN: 1475-2719
  • URL: /core/journals/proceedings-of-the-nutrition-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 11
Total number of PDF views: 47 *
Loading metrics...

Abstract views

Total abstract views: 120 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 21st September 2017. This data will be updated every 24 hours.