{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T16:12:22Z","timestamp":1785946342270,"version":"3.56.0"},"reference-count":111,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T00:00:00Z","timestamp":1590192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondi di Ateneo per la Ricerca di Base, University of Salerno, Italy","award":["ORSA184343"],"award-info":[{"award-number":["ORSA184343"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Celiac disease (CD) is a common intestinal inflammatory disease involving both a genetic background and environmental triggers. The ingestion of gluten, a proteic component of several cereals, represents the main hexogen factor implied in CD onset that involves concomitant innate and adaptive immune responses to gluten. Immunogenicity of some gluten sequences are strongly enhanced as the consequence of the deamidation of specific glutamine residues by type 2 transglutaminase (TG2), a ubiquitous enzyme whose expression is up-regulated in the intestine of CD patients. A short gluten sequence resistant to intestinal proteases, the \u03b1-gliadin peptide 31-43, seems to modulate TG2 function in the gut; on the other hand, the enzyme can affect the biological activity of this peptide. In addition, an intense auto-immune response towards TG2 is a hallmark of CD. Auto-antibodies exert a range of biological effects on several cells, effects that in part overlap with those induced by peptide 31-43. In this review, we delineate a scenario in which TG2, anti-TG2 antibodies and peptide 31-43 closely relate to each other, thus synergistically participating in CD starting and progression.<\/jats:p>","DOI":"10.3390\/ijms21103673","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T06:43:40Z","timestamp":1590389020000},"page":"3673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Interplay between Type 2 Transglutaminase (TG2), Gliadin Peptide 31-43 and Anti-TG2 Antibodies in Celiac Disease"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3720-1442","authenticated-orcid":false,"given":"Stefania","family":"Martucciello","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biology, University of Salerno, 84084 Fisciano (SA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-5513","authenticated-orcid":false,"given":"Silvia","family":"Sposito","sequence":"additional","affiliation":[{"name":"European Laboratory for the Investigation of Food-Induced Diseases (ELFID), University of Salerno, 84084 Fisciano (SA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biology, University of Salerno, 84084 Fisciano (SA), Italy"},{"name":"European Laboratory for the Investigation of Food-Induced Diseases (ELFID), University of Salerno, 84084 Fisciano (SA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2188-3829","authenticated-orcid":false,"given":"Gaetana","family":"Paolella","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biology, University of Salerno, 84084 Fisciano (SA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2825-9711","authenticated-orcid":false,"given":"Ivana","family":"Caputo","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biology, University of Salerno, 84084 Fisciano (SA), Italy"},{"name":"European Laboratory for the Investigation of Food-Induced Diseases (ELFID), University of Salerno, 84084 Fisciano (SA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.coi.2011.08.006","article-title":"Celiac disease and transglutaminase 2: A model for posttranslational modification of antigens and HLA association in the pathogenesis of auto-immune disorders","volume":"23","author":"Sollid","year":"2011","journal-title":"Curr. Opin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20518","DOI":"10.3390\/ijms151120518","article-title":"Gliadin peptides as triggers of the proliferative and stress\/innate immune response of the celiac small intestinal mucosa","volume":"15","author":"Barone","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1007\/s00018-018-2902-0","article-title":"Anti-type 2 transglutaminase antibodies as modulators of type 2 transglutaminase functions: A possible pathological role in celiac disease","volume":"75","author":"Martucciello","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1146\/annurev.immunol.18.1.53","article-title":"Molecular basis of celiac disease","volume":"18","author":"Sollid","year":"2000","journal-title":"Annu. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nrgastro.2015.131","article-title":"Extraintestinal manifestations of coeliac disease","volume":"12","author":"Leffler","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/nm0797-797","article-title":"Identification of tissue transglutaminase as the autoantigen of celiac disease","volume":"3","author":"Dieterich","year":"1997","journal-title":"Nat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1038\/ajg.2010.276","article-title":"Update on serologic testing in celiac disease","volume":"105","author":"Leffler","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/MPG.0b013e318216f2e5","article-title":"ESPGHAN Working Group on Coeliac Disease Diagnosis. Accuracy of diagnostic antibody tests for coeliac disease in children: Summary of an evidence report","volume":"54","author":"Giersiepen","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"917","DOI":"10.2340\/00015555-2162","article-title":"Dermatitis herpetiformis: Pathognomonic transglutaminase IgA deposits in the skin and excellent prognosis on a gluten-free diet","volume":"95","author":"Reunala","year":"2015","journal-title":"Acta Derm. Venereol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/07853890.2016.1222450","article-title":"Dermatitis herpetiformis: A cutaneous manifestation of coeliac disease","volume":"49","author":"Collin","year":"2017","journal-title":"Ann. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/ana.21450","article-title":"Auto-antibodies in gluten ataxia recognize a novel neuronal transglutaminase","volume":"64","author":"Hadjivassiliou","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6900","DOI":"10.3390\/nu7085314","article-title":"Intestinal microbiota and celiac disease: Cause, consequence or co-evolution?","volume":"7","author":"Cenit","year":"2015","journal-title":"Nutrients"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.aah5298","article-title":"Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease","volume":"356","author":"Bouziat","year":"2017","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lerner, A., Ajay, R., and Torsten, M. (2019). The revival of the battle between David and Goliath in the enteric viruses and microbiota struggle: Potential implication for celiac disease. Microorganisms, 7.","DOI":"10.3390\/microorganisms7060173"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s00251-017-0985-7","article-title":"The roles of MHC class II genes and post-translational modification in celiac disease","volume":"69","author":"Sollid","year":"2017","journal-title":"Immunogenetics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1177\/2050640618765506","article-title":"The distribution of HLA DQ2 and DQ8 haplotypes and their association with health indicators in a general Danish population","volume":"6","author":"Thuesen","year":"2018","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Caio, C., Volta, U., Sapone, A., Leffler, D.A., De Giorgio, R., Catassi, C., and Alessio, F. (2019). Celiac disease: A comprehensive current review. BMC Med., 17.","DOI":"10.1186\/s12916-019-1380-z"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.tig.2016.02.003","article-title":"Understanding celiac disease by genomics","volume":"32","author":"Withoff","year":"2016","journal-title":"Trends Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.fm.2006.07.004","article-title":"Chemistry of gluten proteins","volume":"24","author":"Wieser","year":"2007","journal-title":"Food Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00251-012-0599-z","article-title":"Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules","volume":"64","author":"Sollid","year":"2012","journal-title":"Immunogenetics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00251-019-01141-w","article-title":"Update 2020: Nomenclature and listing of celiac disease-relevant gluten epitopes recognized by CD4(+) T cells","volume":"72","author":"Sollid","year":"2020","journal-title":"Immunogenetics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1126\/science.1074129","article-title":"Structural basis for gluten intolerance in celiac sprue","volume":"297","author":"Shan","year":"2002","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.imlet.2005.02.017","article-title":"Adaptive and innate immune responses in celiac disease","volume":"99","author":"Gianfrani","year":"2005","journal-title":"Immunol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jchromb.2007.05.009","article-title":"Identification of a peptide from alpha-gliadin resistant to digestive enzymes: Implications for celiac disease","volume":"855","author":"Mamone","year":"2007","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1021\/jf505461x","article-title":"Tracking the fate of pasta (T. Durum semolina) immunogenic proteins by in vitro simulated digestion","volume":"63","author":"Mamone","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Itzlinger, A., Branchi, F., Elli, L., and Schumann, M. (2018). Gluten-Free Diet in Celiac Disease\u2014Forever and for All?. Nutrients, 10.","DOI":"10.3390\/nu10111796"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/nrm1014","article-title":"Transglutaminases: Crosslinking enzymes with pleiotropic functions","volume":"4","author":"Lorand","year":"2003","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_28","first-page":"1","article-title":"Review transglutaminases: Part II-industrial applications in food, biotechnology, textiles and leather products","volume":"36","author":"Duarte","year":"2019","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1152\/physrev.00016.2010","article-title":"Factor XIII: A coagulation factor with multiple plasmatic and cellular functions","volume":"91","author":"Muszbek","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1152\/physrev.00019.2013","article-title":"Transglutaminase regulation of cell function","volume":"94","author":"Eckert","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-394305-7.00001-X","article-title":"Cellular functions of tissue transglutaminase","volume":"294","author":"Nurminskaya","year":"2012","journal-title":"Int. Rev. Cell. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zemskov, E.A., Mikhailenko, I., Hsia, R.C., Zaritskaya, L., and Belkin, A.M. (2011). Unconventional secretion of tissue transglutaminase involves phospholipid-dependent delivery into recycling endosomes. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019414"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s00726-016-2270-8","article-title":"Role of tissue transglutaminase-2 (TG2)-mediated aminylation in biological processes","volume":"49","author":"Lai","year":"2017","journal-title":"Amino Acids"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1016\/j.bbapap.2008.08.011","article-title":"The propensity for deamidation and transamidation of peptides by transglutaminase 2 is dependent on substrate affinity and reaction conditions","volume":"1784","author":"Stamnaes","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1073\/pnas.042454899","article-title":"Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity","volume":"99","author":"Liu","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Pinkas, D.M., Strop, P., Brunger, A.T., and Khosla, C. (2007). Transglutaminase 2 undergoes a large conformational change upon activation. PLoS Biol., 5.","DOI":"10.1371\/journal.pbio.0050327"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"37866","DOI":"10.1074\/jbc.M111.287490","article-title":"Activation of extracellular transglutaminase 2 by thioredoxin","volume":"286","author":"Jin","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1074\/jbc.RA117.001382","article-title":"Endoplasmic reticulum-resident protein 57 (ERp57) oxidatively inactivates human transglutaminase 2","volume":"293","author":"Yi","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1126\/science.7911253","article-title":"Gh: A GTP-binding protein with transglutaminase activity and receptor signaling function","volume":"264","author":"Nakaoka","year":"1994","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.2741\/4536","article-title":"Tissue transglutaminase (TG2) and mitochondrial function and dysfunction","volume":"22","author":"Lai","year":"2017","journal-title":"Front. Biosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00726-011-1139-0","article-title":"Tissue transglutaminase, inflammation, and cancer: How intimate is the relationship?","volume":"44","author":"Kumar","year":"2013","journal-title":"Amino Acids"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1096\/fj.201801544R","article-title":"Transglutaminase diseases: From biochemistry to the bedside","volume":"33","author":"Lorand","year":"2019","journal-title":"FASEB J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1111\/j.1572-0241.2003.07582.x","article-title":"Expression and enzymatic activity of small intestinal tissue transglutaminase in celiac disease","volume":"98","author":"Esposito","year":"2003","journal-title":"Am. J. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.dld.2006.05.021","article-title":"Transglutaminase 2 in the enterocytes is coeliac specific and gluten dependent","volume":"38","author":"Biagi","year":"2006","journal-title":"Dig. Liver Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/j.1582-4934.2008.00325.x","article-title":"Mucosal tissue transglutaminase expression in celiac disease","volume":"13","author":"Villanacci","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1053\/j.gastro.2005.07.054","article-title":"Unexpected role of surface transglutaminase type II in celiac disease","volume":"129","author":"Maiuri","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1136\/gut.41.6.851","article-title":"Auto-antibodies in celiac disease: Tissue transglutaminase\u2013guilt by association?","volume":"41","author":"Sollid","year":"1997","journal-title":"Gut"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s12026-013-8420-0","article-title":"A subset of anti-rotavirus antibodies directed against the viral protein VP7 predicts the onset of celiac disease and induces typical features of the disease in the intestinal epithelial cell line T84","volume":"56","author":"Dolcino","year":"2013","journal-title":"Immunol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.smim.2015.11.001","article-title":"Celiac disease: Autoimmunity in response to food antigen","volume":"27","author":"Stamnaes","year":"2015","journal-title":"Semin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1542\/peds.2010-3762","article-title":"Specific celiac disease antibodies in children on a gluten-free diet","volume":"128","author":"HogenEsch","year":"2011","journal-title":"Pediatrics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1080\/00365520510023422","article-title":"Small-bowel mucosal transglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: A prospective and randomized clinical study","volume":"40","author":"Kaukinen","year":"2005","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1136\/gutjnl-2011-301346","article-title":"The Oslo definitions for coeliac disease and related terms","volume":"62","author":"Ludvigsson","year":"2013","journal-title":"Gut"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1365-2249.2012.04673.x","article-title":"Intestinal anti-tissue transglutaminase antibodies in potential coeliac disease","volume":"171","author":"Tosco","year":"2012","journal-title":"Clin. Exp. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Maglio, M., Ziberna, F., Aitoro, R., Discepolo, V., Lania, G., Bassi, V., Miele, E., Not, T., Troncone, R., and Auricchio, R. (2017). Intestinal production of anti-tissue transglutaminase 2 antibodies in patients with diagnosis otherthanC celiac disease. Nutrients, 9.","DOI":"10.3390\/nu9101050"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1365-2249.2009.04077.x","article-title":"High density of intraepithelial gammadelta lymphocytes and deposits of immunoglobulin (Ig)M anti-tissue transglutaminase antibodies in the jejunum of coeliac patients with IgA deficiency","volume":"160","author":"Borrelli","year":"2010","journal-title":"Clin. Exp. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.bbadis.2010.05.010","article-title":"Celiac anti-tissuetransglutaminaseantibodiesinterfere with the uptake of alphagliadin peptide 31\u201343 butnot of peptide 57\u201368 by epithelialcells","volume":"1802","author":"Caputo","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00726-011-1120-y","article-title":"Anti-tissue transglutaminase antibodies activate intracellular tissue transglutaminase by modulating cytosolic Ca2+ homeostasis","volume":"44","author":"Caputo","year":"2013","journal-title":"Amino Acids"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s00109-011-0853-0","article-title":"RhoB is associated with the antiangiogenic effects of celiac patient transglutaminase 2-targeted autoantibodies","volume":"90","author":"Martucciello","year":"2012","journal-title":"J. Mol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s00018-013-1455-5","article-title":"CeliacdiseasepatientIgAantibodies induce endothelialadhesion and cellpolarizationdefects via extracellulartransglutaminase 2","volume":"71","author":"Nadalutti","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00726-016-2306-0","article-title":"Transglutaminase 2-specific coeliacdisease auto-antibodies induce morphologicalchanges and signs of inflammation in the small-bowel mucosa of mice","volume":"49","author":"Kalliokoski","year":"2017","journal-title":"Amino Acids"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.4049\/jimmunol.1800819","article-title":"A functional idiotype\/anti-idiotype network is active in genetically gluten-intolerant individuals negative for both celiac disease-related intestinal damage and serum autoantibodies","volume":"202","author":"Quaglia","year":"2019","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1136\/gut.52.2.218","article-title":"Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function","volume":"52","author":"Clemente","year":"2003","journal-title":"Gut"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.4049\/jimmunol.176.4.2512","article-title":"Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: Role of the innate immune response in Celiac disease","volume":"176","author":"Thomas","year":"2006","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40348-015-0029-z","article-title":"Endocytosis and transcytosis of gliadin peptides","volume":"3","author":"Barone","year":"2016","journal-title":"Mol. Cell. Pediatr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fimmu.2019.00031","article-title":"p31-43 Gliadin peptide formsoligomers and induces NLRP3 inflammasome\/caspase 1-dependentmucosaldamage in small intestine","volume":"10","author":"Herrera","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1111\/febs.15109","article-title":"Structural conformation and self-assembly process of p31\u201343 gliadin peptide in aqueous solution. Implications for celiac disease","volume":"287","author":"Herrera","year":"2020","journal-title":"FEBS J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1021\/jf3045523","article-title":"Structural analysis and Caco-2 cell permeability of the celiac-toxic A-gliadin peptide 31-55","volume":"61","author":"Iacomino","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.3389\/fimmu.2019.02792","article-title":"Commentary: p31\u201343 gliadin peptide forms oligomers and induces NLRP3 inflammasome\/caspase 1-dependent mucosal damage in small intestine","volume":"10","author":"Barrera","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e3161","DOI":"10.1002\/psc.3161","article-title":"Structural insights on P31\u201343, a gliadin peptide able to promote an innate but not an adaptive response in celiac disease","volume":"25","author":"Calvanese","year":"2019","journal-title":"J. Pept. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zimmermann, C., Rudloff, S., Lochnit, G., Arampatzi, S., Maison, W., and Zimmer, K.P. (2014). Epithelial transport of immunogenic and toxic gliadin peptides in vitro. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113932"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Barone, M.V., Nanayakkara, M., Paolella, G., Maglio, M., Vitale, V., Troiano, R., Ribecco, M.T., Lania, G., Zanzi, D., and Santagata, S. (2010). Gliadin peptide P31\u201343 localises to endocytic vesicles and interferes with their maturation. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012246"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1136\/gut.2008.169656","article-title":"Endocytotic segregation of gliadin peptide 31\u201349 in enterocytes","volume":"59","author":"Zimmer","year":"2010","journal-title":"Gut"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1053\/j.gastro.2012.05.051","article-title":"Interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affectpermeabilityofintestinalepithelialcellstogliadinpeptides","volume":"143","author":"Lebreton","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/cbin.10874","article-title":"The toxic alpha-gliadin peptide 31-43 enters cells without a surface membrane receptor","volume":"42","author":"Paolella","year":"2018","journal-title":"Cell. Biol. Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1002\/jmr.987","article-title":"Interaction of \u2018toxic\u2019 and \u2018immunogenic\u2019 A-gliadin peptides with a membrane-mimetic environment","volume":"23","author":"Vilasi","year":"2010","journal-title":"J. Mol. Recognit."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/j.febslet.2013.04.031","article-title":"Cell-penetrating peptides: 20 years later, where do we stand?","volume":"587","author":"Bechara","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1016\/j.bbamem.2016.05.021","article-title":"SAP(E)-A cell-penetrating polyproline helix at lipid interfaces","volume":"1858","author":"Franz","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1038\/s41598-018-38063-8","article-title":"Secondary structures and cell-penetrating abilities of arginine-rich peptide foldamers","volume":"9","author":"Oba","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_79","first-page":"211","article-title":"Cell penetrating peptides: A promising tool for the cellular uptake of macromolecular drugs","volume":"19","author":"Zhu","year":"2018","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Furini, G., and Verderio, E.A. (2019). Spotlight on the transglutaminase 2-heparan sulfate interaction. Med. Sci., 7.","DOI":"10.3390\/medsci7010005"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S0140-6736(03)13803-2","article-title":"Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease","volume":"362","author":"Maiuri","year":"2003","journal-title":"Lancet"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1136\/gut.2005.086637","article-title":"Growth factor-like activity of gliadin, an alimentary protein: Implications for coeliac disease","volume":"56","author":"Barone","year":"2007","journal-title":"Gut"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.3945\/ajcn.112.054544","article-title":"An undigested gliadin peptide activates innate immunity and proliferative signaling in enterocytes: The role in celiac disease","volume":"98","author":"Nanayakkara","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Caputo, I., Secondo, A., Lepretti, M., Paolella, G., Auricchio, S., Barone, M.V., and Esposito, C. (2012). Gliadin peptides induce tissue transglutaminase activation and ER-stress through Ca2+ mobilization in Caco-2 cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045209"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1111\/j.1582-4934.2010.01066.x","article-title":"Gliadin fragments promote migration of dendritic cells","volume":"15","author":"Chladkova","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Nanayakkara, M., Lania, G., Maglio, M., Kosova, R., Sarno, M., Gaito, A., Discepolo, V., Troncone, R., Auricchio, S., and Auricchio, R. (2013). Enterocyte proliferation and signaling are constitutively altered in celiac disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076006"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/s42003-019-0443-1","article-title":"Constitutive alterations in vesicular trafficking increase the sensitivity of cells from celiac disease patients to gliadin","volume":"2","author":"Lania","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1136\/gut.2009.183608","article-title":"Lysosomal accumulation of gliadin p31\u201343 peptide induces oxidative stress and tissue transglutaminase-mediated PPARgamma downregulation in intestinal epithelial cells and coeliac mucosa","volume":"59","author":"Luciani","year":"2010","journal-title":"Gut"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Paolella, G., Nanayakkara, M., Sposito, S., Lepretti, M., Auricchio, S., Esposito, C., Barone, M.V., Martucciello, S., and Caputo, I. (2020). Constitutive differential features of type 2 transglutaminase in cells derived from celiac patients and from healthy subjects. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041231"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/1521-4141(200105)31:5<1317::AID-IMMU1317>3.0.CO;2-I","article-title":"T cells from celiac disease lesions recognize gliadin epitopes deamidated in situ by endogenous tissue transglutaminase","volume":"31","author":"Molberg","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1051\/bmdcn\/2017070315","article-title":"Transglutaminase 2 in human diseases","volume":"7","author":"Szondy","year":"2017","journal-title":"Biomedicine"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1136\/gut.51.2.177","article-title":"Anti-tissue transglutaminase antibodies from coeliac patients inhibit transglutaminase activity both in vitro and in situ","volume":"51","author":"Esposito","year":"2002","journal-title":"Gut"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1136\/gut.52.11.1562","article-title":"Auto-antibodies of patients with coeliac disease are insufficient to block tissue transglutaminase activity","volume":"52","author":"Dieterich","year":"2003","journal-title":"Gut"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1053\/j.gastro.2007.01.030","article-title":"Humoral immune response to tissue transglutaminase is related to epithelial cell proliferation in celiac disease","volume":"132","author":"Barone","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jaut.2006.03.002","article-title":"Coeliac auto-antibodies can enhance transamidating and inhibit GTPase activity of tissue transglutaminase: Dependence on reaction environment and enzyme fitness","volume":"26","author":"Vecsei","year":"2006","journal-title":"J. Autoimmun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s10238-014-0325-2","article-title":"Gliadin-dependen cytokine production in a bidimensional cellular model of celiac intestinal mucosa","volume":"15","author":"Vincentini","year":"2015","journal-title":"Clin. Exp. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s10875-012-9745-5","article-title":"Are transglutaminase 2 inhibitors able to reduce gliadin-induced toxicity related to celiac disease? A proof-of-concept study","volume":"33","author":"Rauhavirta","year":"2013","journal-title":"J. Clin. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00726-016-2339-4","article-title":"Involvement of cell surface TG2 in the aggregation of K562 cells triggered by gluten","volume":"49","author":"Feriotto","year":"2017","journal-title":"Amino Acids"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/pr.2012.4","article-title":"Early tissue transglutaminase-mediated response underlies K562(S)-cell gliadin-dependent agglutination","volume":"71","author":"Silano","year":"2012","journal-title":"Pediatr. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"15146","DOI":"10.1038\/s41598-017-14845-4","article-title":"The gliadin peptide 31-43 exacerbates kainate neurotoxicity in epilepsy models","volume":"7","author":"Gerace","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/s41586-020-2003-8","article-title":"IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease","volume":"578","author":"Abadie","year":"2020","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"9042","DOI":"10.1021\/jm501145a","article-title":"Discovery of potent and specific dihydroisoxazole inhibitors of human transglutaminase 2","volume":"57","author":"Herrera","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1365-2249.2010.04317.x","article-title":"Epithelial transport and deamidation of gliadin peptides: A role for coeliac disease patient immunoglobulin A","volume":"164","author":"Rauhavirta","year":"2011","journal-title":"Clin. Exp. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e100101","DOI":"10.15252\/embj.2018100101","article-title":"A pathogenic role for cystic fibrosis trans membrane conductance regulator in celiac disease","volume":"38","author":"Villella","year":"2019","journal-title":"EMBO J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1080\/003655299750024896","article-title":"31\u201343 amino acid sequence of the alpha-gliadin induces anti-endomysial antibody production during in vitro challenge","volume":"34","author":"Picarelli","year":"1999","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Paolella, G., Caputo, I., Marabotti, A., Lepretti, M., Salzano, A.M., Scaloni, A., Vitale, M., Zambrano, N., Sblattero, D., and Esposito, C. (2013). Celiac anti-type 2 transglutaminase antibodies induce phosphoproteome modification in intestinal epithelial Caco-2 cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0084403"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Nanayakkara, M., Kosova, R., Lania, G., Sarno, M., Gaito, A., Galatola, M., Greco, L., Cuomo, M., Troncone, R., and Auricchio, S. (2013). A celiac cellular phenotype, with altered LPP sub-cellular distribution, is inducible in controls by the toxic gliadin peptide P31-43. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079763"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1053\/j.gastro.2007.04.070","article-title":"Sera of patients with celiac disease and neurologic disorders evoke a mitochondrial-dependent apoptosis in vitro","volume":"133","author":"Cervio","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s00726-016-2307-z","article-title":"Celiac anti-type 2 transglutaminase antibodies induce differential effects in fibroblasts from celiac disease patients and from healthy subjects","volume":"49","author":"Paolella","year":"2017","journal-title":"Amino Acids"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/gut.2003.024836","article-title":"In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac auto-antibodies","volume":"53","author":"Halttunen","year":"2004","journal-title":"Gut"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1136\/gutjnl-2015-310148","article-title":"Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing","volume":"66","author":"Moreno","year":"2017","journal-title":"Gut"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/10\/3673\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:31:48Z","timestamp":1760175108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/10\/3673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,23]]},"references-count":111,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["ijms21103673"],"URL":"https:\/\/doi.org\/10.3390\/ijms21103673","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,23]]}}}