{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:25:03Z","timestamp":1762543503212,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PROGRES Q 36 - Metabolism, and 260531\/SVV\/2020: Multidisciplinary research of the regulation mechanisms of human metabolism.","award":["260531\/SVV\/2020:"],"award-info":[{"award-number":["260531\/SVV\/2020:"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The autoimmune condition, Celiac Disease (CeD), displays broad clinical symptoms due to gluten exposure. Its genetic association with DQ variants in the human leukocyte antigen (HLA) system has been recognised. Monocyte-derived mature dendritic cells (MoDCs) present gluten peptides through HLA-DQ and co-stimulatory molecules to T lymphocytes, eliciting a cytokine-rich microenvironment. Having access to CeD associated families prevalent in the Czech Republic, this study utilised an in vitro model to investigate their differential monocyte profile. The higher monocyte yields isolated from PBMCs of CeD patients versus control individuals also reflected the greater proportion of dendritic cells derived from these sources following lipopolysaccharide (LPS)\/ peptic-tryptic-gliadin (PTG) fragment stimulation. Cell surface markers of CeD monocytes and MoDCs were subsequently profiled. This foremost study identified a novel bio-profile characterised by elevated CD64 and reduced CD33 levels, unique to CD14++ monocytes of CeD patients. Normalisation to LPS stimulation revealed the increased sensitivity of CeD-MoDCs to PTG, as shown by CD86 and HLA-DQ flow cytometric readouts. Enhanced CD86 and HLA-DQ expression in CeD-MoDCs were revealed by confocal microscopy. Analysis highlighted their dominance at the CeD-MoDC membrane in comparison to controls, reflective of superior antigen presentation ability. In conclusion, this investigative study deciphered the monocytes and MoDCs of CeD patients with the identification of a novel bio-profile marker of potential diagnostic value for clinical interpretation. Herein, the characterisation of CD86 and HLA-DQ as activators to stimulants, along with robust membrane assembly reflective of efficient antigen presentation, offers CeD targeted therapeutic avenues worth further exploration.<\/jats:p>","DOI":"10.3390\/ijms22189982","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T12:00:44Z","timestamp":1631707244000},"page":"9982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Celiac Disease Defined by Over-Sensitivity to Gliadin Activation and Superior Antigen Presentation of Dendritic Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6593-9911","authenticated-orcid":false,"given":"Michael","family":"Hudec","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Third Faculty of Medicine, Charles University, Rusk\u00e1 87, 100 00 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamila","family":"Riegerov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Immunology and Clinical Biochemistry, Third Faculty of Medicine, Charles University, Rusk\u00e1 87, 100 00 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9171-9800","authenticated-orcid":false,"given":"Jan","family":"Pala","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Third Faculty of Medicine, Charles University, Rusk\u00e1 87, 100 00 Prague, Czech Republic"},{"name":"Department of Experimental Neurobiology, National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viera","family":"K\u00fatna","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurobiology, National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1208-5588","authenticated-orcid":false,"given":"Marie","family":"\u010cern\u00e1","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Third Faculty of Medicine, Charles University, Rusk\u00e1 87, 100 00 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1171-9830","authenticated-orcid":false,"given":"Valerie Br\u00edd","family":"O\u00b4Leary","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Third Faculty of Medicine, Charles University, Rusk\u00e1 87, 100 00 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrgastro.2015.136","article-title":"Coeliac disease and autoimmune disease-genetic overlap and screening","volume":"12","author":"Lundin","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/jhg.2008.5","article-title":"The HLA genomic loci map: Expression, interaction, diversity and disease","volume":"54","author":"Shiina","year":"2009","journal-title":"J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.humimm.2016.02.003","article-title":"HLA-DRB1, -DQA1 and -DQB1 genotyping of 180 Czech individuals from the Czech Republic pop 3","volume":"77","author":"Zajacova","year":"2016","journal-title":"Hum. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S0140-6736(17)31796-8","article-title":"Coeliac disease","volume":"391","author":"Lebwohl","year":"2018","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/S0140-6736(96)70237-4","article-title":"Coeliac disease","volume":"349","author":"Maki","year":"1997","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/0016-5085(92)91819-P","article-title":"Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (\u2018celiac sprue\u2019)","volume":"102","author":"Marsh","year":"1992","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nri885","article-title":"Coeliac disease: Dissecting a complex inflammatory disorder","volume":"2","author":"Sollid","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","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_9","first-page":"143","article-title":"Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease","volume":"205","author":"Moura","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1749-6632.2009.04037.x","article-title":"Tight junctions, intestinal permeability, and autoimmunity: Celiac disease and type 1 diabetes paradigms","volume":"1165","author":"Visser","year":"2009","journal-title":"Ann. Acad. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jcmgh.2016.12.006","article-title":"Celiac Disease: Role of the Epithelial Barrier","volume":"3","author":"Schumann","year":"2017","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1146\/annurev.immunol.18.1.767","article-title":"Immunobiology of Dendritic Cells","volume":"18","author":"Banchereau","year":"2000","journal-title":"Annu. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7038","DOI":"10.4049\/jimmunol.175.10.7038","article-title":"Gliadin Fragments Induce Phenotypic and Functional Maturation of Human Dendritic Cells","volume":"175","year":"2005","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1084\/jem.20061011","article-title":"Monocytes give rise to mucosal, but not splenic, conventional dendritic cells","volume":"204","author":"Varol","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.immuni.2012.12.001","article-title":"Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis","volume":"38","author":"Yona","year":"2013","journal-title":"Immunity"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1182\/blood-2010-12-326355","article-title":"Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets","volume":"118","author":"Wong","year":"2011","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12026-012-8297-3","article-title":"The three human monocyte subsets: Implications for health and disease","volume":"53","author":"Wong","year":"2012","journal-title":"Immunol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.1182\/blood-2011-01-326827","article-title":"SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset","volume":"118","author":"Zawada","year":"2011","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s10875-006-9061-z","article-title":"Gliadin Peptides Activate Blood Monocytes from Patients with Celiac Disease","volume":"27","author":"Cinova","year":"2007","journal-title":"J. Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1097\/MCG.0000000000000919","article-title":"World Gastroenterology Organisation Global Guidelines","volume":"51","author":"Bai","year":"2017","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kleiveland, C.R. (2015). Peripheral Blood Mononuclear Cells. The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models, Springer.","DOI":"10.1007\/978-3-319-16104-4_15"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gren, S.T., Rasmussen, T.B., Janciauskiene, S., H\u00e5kansson, K., Gerwien, J.G., and Grip, O. (2015). A Single-Cell Gene-Expression Profile Reveals Inter-Cellular Heterogeneity within Human Monocyte Subsets. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144351"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1038\/leu.2015.52","article-title":"CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia","volume":"29","author":"Kenderian","year":"2015","journal-title":"Leuk."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Akinrinmade, O.A., Chetty, S., Daramola, A.K., Islam, M.-U., Thepen, T., and Barth, S. (2017). CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases. Biomed., 5.","DOI":"10.3390\/biomedicines5030056"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"415","DOI":"10.3109\/10428199709039028","article-title":"CD11c Integrin Gene Promoter Activity during Myeloid Differentiation","volume":"25","year":"1997","journal-title":"Leuk. Lymphoma"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.3389\/fimmu.2017.00327","article-title":"The Role of Dendritic Cell Maturation in the Induction of Insulin-Dependent Diabetes Mellitus","volume":"8","author":"Mbongue","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/tropej\/fmq041","article-title":"Familial Prevalence of Celiac Disease","volume":"57","author":"Thapa","year":"2010","journal-title":"J. Trop. Pediatr."},{"key":"ref_28","unstructured":"(2009). Title Page\/List of Contents\/Preface, S. Karger AG."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1600-065X.1999.tb01307.x","article-title":"HLA class II transgenic mice as models of human diseases","volume":"169","author":"Taneja","year":"1999","journal-title":"Immunol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"587","DOI":"10.3109\/07853890.2010.505931","article-title":"The prevalence of celiac disease in Europe: Results of a centralized, international mass screening project","volume":"42","author":"Mustalahti","year":"2010","journal-title":"Ann. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.dld.2008.03.013","article-title":"Undetected coeliac disease in the elderly: A biopsy-proven population-based study","volume":"40","author":"Vilppula","year":"2008","journal-title":"Dig. Liver Dis."},{"key":"ref_32","first-page":"1426","article-title":"HLA\u2014DQA1*05-DQB1*0201 positivity predisposes to coeliac disease in Czech diabetic children","volume":"89","author":"Cinek","year":"2007","journal-title":"Acta Paediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"h4347","DOI":"10.1136\/bmj.h4347","article-title":"Celiac disease and non-celiac gluten sensitivity","volume":"351","author":"Lebwohl","year":"2015","journal-title":"BMJ"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1097\/MPG.0b013e318181afed","article-title":"Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition Consensus Report on Celiac Disease","volume":"47","author":"Fasano","year":"2008","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.dld.2007.10.004","article-title":"The incidence of coeliac disease in adult first degree relatives","volume":"40","author":"Biagi","year":"2008","journal-title":"Dig. Liver Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1056\/NEJMoa1400697","article-title":"Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children","volume":"371","author":"Lionetti","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1136\/gut.52.2.168","article-title":"European and North American populations should be screened for coeliac disease","volume":"52","author":"Fasano","year":"2003","journal-title":"Gut"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1177\/2050640619836057","article-title":"Celiac disease-on-chip: Modeling a multifactorial disease in vitro","volume":"7","author":"Moerkens","year":"2019","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/17474124.2021.1850262","article-title":"The use of peripheral blood mononuclear cells in celiac disease diagnosis and treatment","volume":"15","author":"Kurki","year":"2021","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/ajg.2011.24","article-title":"CD62LnegCD38+ Expression on Circulating CD4+ T Cells Identifies Mucosally Differentiated Cells in Protein Fed Mice and in Human Celiac Disease Patients and Controls","volume":"106","author":"Broere","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1111\/jnc.15327","article-title":"Microglial phagocytosis of neurons in neurodegeneration, and its regulation","volume":"158","author":"Butler","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13024-021-00443-6","article-title":"The CD33 short isoform is a gain-of-function variant that enhances A\u03b21\u201342 phagocytosis in microglia","volume":"16","author":"Bhattacherjee","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1203\/01.PDR.0000142586.47798.5E","article-title":"Neutrophil CD64 Is a Sensitive Diagnostic Marker for Early-Onset Neonatal Infection","volume":"56","author":"Ng","year":"2004","journal-title":"Pediatr. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"438","DOI":"10.3389\/fimmu.2020.00438","article-title":"Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells","volume":"11","author":"Azeem","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1053\/j.gastro.2006.06.002","article-title":"A Unique Dendritic Cell Subset Accumulates in the Celiac Lesion and Efficiently Activates Gluten-Reactive T Cells","volume":"131","author":"Tollefsen","year":"2006","journal-title":"Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.molimm.2005.02.016","article-title":"Molecular cloning, expression and functional characterization of miniature swine CD86","volume":"43","author":"Choi","year":"2006","journal-title":"Mol. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.trim.2005.03.021","article-title":"HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms","volume":"14","author":"Thorsby","year":"2005","journal-title":"Transpl. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S1074-7613(00)00030-3","article-title":"Soluble CD86 Is a Costimulatory Molecule for Human T Lymphocytes","volume":"13","author":"Jeannin","year":"2000","journal-title":"Immunity"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/MPG.0000000000002497","article-title":"European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020","volume":"70","author":"Husby","year":"2020","journal-title":"J. Pediatr. Gastroenterol. Nutr."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9982\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:00:20Z","timestamp":1760166020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9982"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,15]]},"references-count":49,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22189982"],"URL":"https:\/\/doi.org\/10.3390\/ijms22189982","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,9,15]]}}}