Pediatric Celiac Disease Patients Show Alterations of Dendritic Cell Shape and Actin Rearrangement
Celiac disease (CD) is a frequent intestinal inflammatory disease occurring in genetically susceptible individuals upon gluten ingestion. Recent studies point to a role in CD for genes involved in cell shape, adhesion and actin rearrangements, including a Rho family regulator, Rho GTPase-activating...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-03-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/5/2708 |
id |
doaj-8ae282c4d8fd45c396219d8c4a06f1b2 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valentina Discepolo Giuliana Lania Maria Leonarda Gertrude Ten Eikelder Merlin Nanayakkara Leandra Sepe Rossella Tufano Riccardo Troncone Salvatore Auricchio Renata Auricchio Giovanni Paolella Maria Vittoria Barone |
spellingShingle |
Valentina Discepolo Giuliana Lania Maria Leonarda Gertrude Ten Eikelder Merlin Nanayakkara Leandra Sepe Rossella Tufano Riccardo Troncone Salvatore Auricchio Renata Auricchio Giovanni Paolella Maria Vittoria Barone Pediatric Celiac Disease Patients Show Alterations of Dendritic Cell Shape and Actin Rearrangement International Journal of Molecular Sciences celiac disease dendritic cells actin cytoskeleton cell shape adhesion fibronectin |
author_facet |
Valentina Discepolo Giuliana Lania Maria Leonarda Gertrude Ten Eikelder Merlin Nanayakkara Leandra Sepe Rossella Tufano Riccardo Troncone Salvatore Auricchio Renata Auricchio Giovanni Paolella Maria Vittoria Barone |
author_sort |
Valentina Discepolo |
title |
Pediatric Celiac Disease Patients Show Alterations of Dendritic Cell Shape and Actin Rearrangement |
title_short |
Pediatric Celiac Disease Patients Show Alterations of Dendritic Cell Shape and Actin Rearrangement |
title_full |
Pediatric Celiac Disease Patients Show Alterations of Dendritic Cell Shape and Actin Rearrangement |
title_fullStr |
Pediatric Celiac Disease Patients Show Alterations of Dendritic Cell Shape and Actin Rearrangement |
title_full_unstemmed |
Pediatric Celiac Disease Patients Show Alterations of Dendritic Cell Shape and Actin Rearrangement |
title_sort |
pediatric celiac disease patients show alterations of dendritic cell shape and actin rearrangement |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-03-01 |
description |
Celiac disease (CD) is a frequent intestinal inflammatory disease occurring in genetically susceptible individuals upon gluten ingestion. Recent studies point to a role in CD for genes involved in cell shape, adhesion and actin rearrangements, including a Rho family regulator, Rho GTPase-activating protein 31 (ARHGAP31). In this study, we investigated the morphology and actin cytoskeletons of peripheral monocyte-derived dendritic cells (DCs) from children with CD and controls when in contact with a physiological substrate, fibronectin. DCs were generated from peripheral blood monocytes of pediatric CD patients and controls. After adhesion on fibronectin, DCs showed a higher number of protrusions and a more elongated shape in CD patients compared with controls, as assessed by immunofluorescence actin staining, transmitted light staining and video time-lapse microscopy. These alterations did not depend on active intestinal inflammation associated with gluten consumption and were specific to CD, since they were not found in subjects affected by other intestinal inflammatory conditions. The elongated morphology was not a result of differences in DC activation or maturation status, and did not depend on the human leukocyte antigen (HLA)-DQ2 haplotype. Notably, we found that ARH-GAP31 mRNA levels were decreased while RhoA-GTP activity was increased in CD DCs, pointing to an impairment of the Rho pathway in CD cells. Accordingly, Rho inhibition was able to prevent the cytoskeleton rearrangements leading to the elongated morphology of celiac DCs upon adhesion on fibronectin, confirming the role of this pathway in the observed phenotype. In conclusion, adhesion on fibronectin discriminated CD from the controls’ DCs, revealing a gluten-independent CD-specific cellular phenotype related to DC shape and regulated by RhoA activity. |
topic |
celiac disease dendritic cells actin cytoskeleton cell shape adhesion fibronectin |
url |
https://www.mdpi.com/1422-0067/22/5/2708 |
work_keys_str_mv |
AT valentinadiscepolo pediatricceliacdiseasepatientsshowalterationsofdendriticcellshapeandactinrearrangement AT giulianalania pediatricceliacdiseasepatientsshowalterationsofdendriticcellshapeandactinrearrangement AT marialeonardagertrudeteneikelder pediatricceliacdiseasepatientsshowalterationsofdendriticcellshapeandactinrearrangement AT merlinnanayakkara pediatricceliacdiseasepatientsshowalterationsofdendriticcellshapeandactinrearrangement AT leandrasepe pediatricceliacdiseasepatientsshowalterationsofdendriticcellshapeandactinrearrangement AT rossellatufano pediatricceliacdiseasepatientsshowalterationsofdendriticcellshapeandactinrearrangement AT riccardotroncone pediatricceliacdiseasepatientsshowalterationsofdendriticcellshapeandactinrearrangement AT salvatoreauricchio pediatricceliacdiseasepatientsshowalterationsofdendriticcellshapeandactinrearrangement AT renataauricchio pediatricceliacdiseasepatientsshowalterationsofdendriticcellshapeandactinrearrangement AT giovannipaolella pediatricceliacdiseasepatientsshowalterationsofdendriticcellshapeandactinrearrangement AT mariavittoriabarone pediatricceliacdiseasepatientsshowalterationsofdendriticcellshapeandactinrearrangement |
_version_ |
1724228567254958080 |
spelling |
doaj-8ae282c4d8fd45c396219d8c4a06f1b22021-03-09T00:00:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01222708270810.3390/ijms22052708Pediatric Celiac Disease Patients Show Alterations of Dendritic Cell Shape and Actin RearrangementValentina Discepolo0Giuliana Lania1Maria Leonarda Gertrude Ten Eikelder2Merlin Nanayakkara3Leandra Sepe4Rossella Tufano5Riccardo Troncone6Salvatore Auricchio7Renata Auricchio8Giovanni Paolella9Maria Vittoria Barone10European Laboratory for the Investigation of Food Induced Diseases, Department of Translational Medical Science, Section of Pediatrics, and ELFID, University Federico II, Via S. Pansini 5, 80131 Naples, ItalyEuropean Laboratory for the Investigation of Food Induced Diseases, Department of Translational Medical Science, Section of Pediatrics, and ELFID, University Federico II, Via S. Pansini 5, 80131 Naples, ItalyDepartment of Gynecology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsEuropean Laboratory for the Investigation of Food Induced Diseases, Department of Translational Medical Science, Section of Pediatrics, and ELFID, University Federico II, Via S. Pansini 5, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, ItalyEuropean Laboratory for the Investigation of Food Induced Diseases, Department of Translational Medical Science, Section of Pediatrics, and ELFID, University Federico II, Via S. Pansini 5, 80131 Naples, ItalyEuropean Laboratory for the Investigation of Food Induced Diseases, Department of Translational Medical Science, Section of Pediatrics, and ELFID, University Federico II, Via S. Pansini 5, 80131 Naples, ItalyEuropean Laboratory for the Investigation of Food Induced Diseases, Department of Translational Medical Science, Section of Pediatrics, and ELFID, University Federico II, Via S. Pansini 5, 80131 Naples, ItalyEuropean Laboratory for the Investigation of Food Induced Diseases, Department of Translational Medical Science, Section of Pediatrics, and ELFID, University Federico II, Via S. Pansini 5, 80131 Naples, ItalyEuropean Laboratory for the Investigation of Food Induced Diseases, Department of Translational Medical Science, Section of Pediatrics, and ELFID, University Federico II, Via S. Pansini 5, 80131 Naples, ItalyCeliac disease (CD) is a frequent intestinal inflammatory disease occurring in genetically susceptible individuals upon gluten ingestion. Recent studies point to a role in CD for genes involved in cell shape, adhesion and actin rearrangements, including a Rho family regulator, Rho GTPase-activating protein 31 (ARHGAP31). In this study, we investigated the morphology and actin cytoskeletons of peripheral monocyte-derived dendritic cells (DCs) from children with CD and controls when in contact with a physiological substrate, fibronectin. DCs were generated from peripheral blood monocytes of pediatric CD patients and controls. After adhesion on fibronectin, DCs showed a higher number of protrusions and a more elongated shape in CD patients compared with controls, as assessed by immunofluorescence actin staining, transmitted light staining and video time-lapse microscopy. These alterations did not depend on active intestinal inflammation associated with gluten consumption and were specific to CD, since they were not found in subjects affected by other intestinal inflammatory conditions. The elongated morphology was not a result of differences in DC activation or maturation status, and did not depend on the human leukocyte antigen (HLA)-DQ2 haplotype. Notably, we found that ARH-GAP31 mRNA levels were decreased while RhoA-GTP activity was increased in CD DCs, pointing to an impairment of the Rho pathway in CD cells. Accordingly, Rho inhibition was able to prevent the cytoskeleton rearrangements leading to the elongated morphology of celiac DCs upon adhesion on fibronectin, confirming the role of this pathway in the observed phenotype. In conclusion, adhesion on fibronectin discriminated CD from the controls’ DCs, revealing a gluten-independent CD-specific cellular phenotype related to DC shape and regulated by RhoA activity.https://www.mdpi.com/1422-0067/22/5/2708celiac diseasedendritic cellsactin cytoskeletoncell shapeadhesionfibronectin |