PMID- 34576145
OWN - NLM
STAT- MEDLINE
DCOM- 20211019
LR  - 20211019
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 18
DP  - 2021 Sep 15
TI  - Celiac Disease Defined by Over-Sensitivity to Gliadin Activation and Superior 
      Antigen Presentation of Dendritic Cells.
LID - 10.3390/ijms22189982 [doi]
LID - 9982
AB  - 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.
FAU - Hudec, Michael
AU  - Hudec M
AUID- ORCID: 0000-0002-6593-9911
AD  - Department of Medical Genetics, Third Faculty of Medicine, Charles University, 
      Ruska 87, 100 00 Prague, Czech Republic.
FAU - Riegerova, Kamila
AU  - Riegerova K
AD  - Department of Immunology and Clinical Biochemistry, Third Faculty of Medicine, 
      Charles University, Ruska 87, 100 00 Prague, Czech Republic.
FAU - Pala, Jan
AU  - Pala J
AUID- ORCID: 0000-0001-9171-9800
AD  - Department of Pathophysiology, Third Faculty of Medicine, Charles University, 
      Ruska 87, 100 00 Prague, Czech Republic.
AD  - Department of Experimental Neurobiology, National Institute of Mental Health, 
      Topolova 748, 250 67 Klecany, Czech Republic.
FAU - Kutna, Viera
AU  - Kutna V
AD  - Department of Experimental Neurobiology, National Institute of Mental Health, 
      Topolova 748, 250 67 Klecany, Czech Republic.
FAU - Cerna, Marie
AU  - Cerna M
AUID- ORCID: 0000-0002-1208-5588
AD  - Department of Medical Genetics, Third Faculty of Medicine, Charles University, 
      Ruska 87, 100 00 Prague, Czech Republic.
FAU - O Leary, Valerie Brid
AU  - O Leary VB
AUID- ORCID: 0000-0003-1171-9830
AD  - Department of Medical Genetics, Third Faculty of Medicine, Charles University, 
      Ruska 87, 100 00 Prague, Czech Republic.
LA  - eng
GR  - 260531/SVV/2020:/PROGRES Q 36 - Metabolism, and 260531/SVV/2020: 
      Multidisciplinary research of the regulation mechanisms of human metabolism./
PT  - Journal Article
DEP - 20210915
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antigens, CD)
RN  - 0 (Biomarkers)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (Lipopolysaccharides)
RN  - 9007-90-3 (Gliadin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antigen Presentation/*immunology
MH  - Antigens, CD/metabolism
MH  - Autoimmune Diseases/immunology
MH  - Biomarkers/metabolism
MH  - Celiac Disease/epidemiology/*immunology
MH  - Cell Membrane/metabolism
MH  - Czech Republic/epidemiology
MH  - Dendritic Cells/*immunology
MH  - Disease Susceptibility
MH  - Family
MH  - Female
MH  - Gliadin/*adverse effects
MH  - HLA-DQ Antigens/metabolism
MH  - Humans
MH  - Lipopolysaccharides
MH  - Male
MH  - Middle Aged
MH  - Monocytes/metabolism
MH  - Pedigree
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Young Adult
PMC - PMC8469067
OTO - NOTNLM
OT  - CD33
OT  - CD64
OT  - CD86
OT  - MHCDQ
OT  - autoimmunity
OT  - major histocompatibility complex II
OT  - monocyte
OT  - monocyte-derived dendritic cells
COIS- The authors declare no conflict of interest.
EDAT- 2021/09/29 06:00
MHDA- 2021/10/21 06:00
PMCR- 2021/09/15
CRDT- 2021/09/28 01:18
PHST- 2021/07/30 00:00 [received]
PHST- 2021/09/08 00:00 [revised]
PHST- 2021/09/13 00:00 [accepted]
PHST- 2021/09/28 01:18 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2021/09/15 00:00 [pmc-release]
AID - ijms22189982 [pii]
AID - ijms-22-09982 [pii]
AID - 10.3390/ijms22189982 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Sep 15;22(18):9982. doi: 10.3390/ijms22189982.