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Circulating Dendritic Cells from Celiac Disease Patients Display a Gut-Homing Profile and are Differentially Modulated by Different Gliadin-Derived Peptides.
Mol Nutr Food Res 2020; :e1900989MN

Abstract

SCOPE

Circulating dendritic cell (DC) and monocyte subsets contribute to the pool of intestinal DC and macrophages in celiac disease (CeD), an autoimmune gut disorder triggered by dietary gluten. Here, this study aims to characterize these circulating subsets in CeD and assess the effect of different gliadin-derived peptides on conventional DC (cDC).

METHODS AND RESULTS

Flow cytometry profiling of peripheral blood mononuclear cells reveals a slight decrease in the proportion of plasmacytoid and type 1 cDC in gluten-free diet (GFD)-treated CeD patients. In comparison to healthy donors, DC and monocyte subsets from active and GFD-treated CeD patients display an increased gut-homing profile. Type 2 cDC (cDC2) are sorted and stimulated with the gliadin-derived peptides 8-mer, 19-mer, and 33-mer. All peptides induce cDC2 maturation, although the profile is different. While peptide 8-mer induces a Th1/Th17 pro-inflammatory cytokine profile in active CeD patients, cDC2 primed with peptide 33-mer displays a higher capacity to promote gut-homing CCR9+ expression onto autologous T-cells.

CONCLUSION

Distinct gliadin-derived peptides elicit different effects on cDC2 phenotype and function. This effect is compatible with a model where diverse gliadin peptides may cooperate to promote full cDC2 activation and the subsequent T-cell response in genetically predisposed individuals.

Authors+Show Affiliations

Mucosal Immunology Laboratory, Instituto de Biología y Genética Molecular (IBGM), University of Valladolid-CSIC, C/ Sanz y Forés 3, 47003, Valladolid, Spain. Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.Flow Cytometry facility. Instituto de Biología y Genética Molecular (IBGM), University of Valladolid-CSIC, C/ Sanz y Forés 3, 47003, Valladolid, Spain.Mucosal Immunology Laboratory, Instituto de Biología y Genética Molecular (IBGM), University of Valladolid-CSIC, C/ Sanz y Forés 3, 47003, Valladolid, Spain.Digestive Disease Unit, Hospital Clínico Universitario de Valladolid, Avda Ramón y Cajal 3, 47003, Valladolid, Spain.Mucosal Immunology Laboratory, Instituto de Biología y Genética Molecular (IBGM), University of Valladolid-CSIC, C/ Sanz y Forés 3, 47003, Valladolid, Spain. Laboratory of Molecular Genetics, Hospital Universitario Río Hortega, C/ Dulzaina 2, 47012, Valladolid, Spain.Mucosal Immunology Laboratory, Instituto de Biología y Genética Molecular (IBGM), University of Valladolid-CSIC, C/ Sanz y Forés 3, 47003, Valladolid, Spain.Mucosal Immunology Laboratory, Instituto de Biología y Genética Molecular (IBGM), University of Valladolid-CSIC, C/ Sanz y Forés 3, 47003, Valladolid, Spain.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31970917

Citation

Escudero-Hernández, Celia, et al. "Circulating Dendritic Cells From Celiac Disease Patients Display a Gut-Homing Profile and Are Differentially Modulated By Different Gliadin-Derived Peptides." Molecular Nutrition & Food Research, 2020, pp. e1900989.
Escudero-Hernández C, Martín Á, de Pedro Andrés R, et al. Circulating Dendritic Cells from Celiac Disease Patients Display a Gut-Homing Profile and are Differentially Modulated by Different Gliadin-Derived Peptides. Mol Nutr Food Res. 2020.
Escudero-Hernández, C., Martín, Á., de Pedro Andrés, R., Fernández-Salazar, L., Garrote, J. A., Bernardo, D., & Arranz, E. (2020). Circulating Dendritic Cells from Celiac Disease Patients Display a Gut-Homing Profile and are Differentially Modulated by Different Gliadin-Derived Peptides. Molecular Nutrition & Food Research, pp. e1900989. doi:10.1002/mnfr.201900989.
Escudero-Hernández C, et al. Circulating Dendritic Cells From Celiac Disease Patients Display a Gut-Homing Profile and Are Differentially Modulated By Different Gliadin-Derived Peptides. Mol Nutr Food Res. 2020 Jan 23;e1900989. PubMed PMID: 31970917.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating Dendritic Cells from Celiac Disease Patients Display a Gut-Homing Profile and are Differentially Modulated by Different Gliadin-Derived Peptides. AU - Escudero-Hernández,Celia, AU - Martín,Álvaro, AU - de Pedro Andrés,Rodrigo, AU - Fernández-Salazar,Luis, AU - Garrote,José Antonio, AU - Bernardo,David, AU - Arranz,Eduardo, Y1 - 2020/01/23/ PY - 2019/09/17/received PY - 2019/12/11/revised PY - 2020/1/24/pubmed PY - 2020/1/24/medline PY - 2020/1/24/entrez KW - T cells KW - antigen presentation KW - autoimmune diseases KW - gliadin KW - monocytes SP - e1900989 EP - e1900989 JF - Molecular nutrition & food research JO - Mol Nutr Food Res N2 - SCOPE: Circulating dendritic cell (DC) and monocyte subsets contribute to the pool of intestinal DC and macrophages in celiac disease (CeD), an autoimmune gut disorder triggered by dietary gluten. Here, this study aims to characterize these circulating subsets in CeD and assess the effect of different gliadin-derived peptides on conventional DC (cDC). METHODS AND RESULTS: Flow cytometry profiling of peripheral blood mononuclear cells reveals a slight decrease in the proportion of plasmacytoid and type 1 cDC in gluten-free diet (GFD)-treated CeD patients. In comparison to healthy donors, DC and monocyte subsets from active and GFD-treated CeD patients display an increased gut-homing profile. Type 2 cDC (cDC2) are sorted and stimulated with the gliadin-derived peptides 8-mer, 19-mer, and 33-mer. All peptides induce cDC2 maturation, although the profile is different. While peptide 8-mer induces a Th1/Th17 pro-inflammatory cytokine profile in active CeD patients, cDC2 primed with peptide 33-mer displays a higher capacity to promote gut-homing CCR9+ expression onto autologous T-cells. CONCLUSION: Distinct gliadin-derived peptides elicit different effects on cDC2 phenotype and function. This effect is compatible with a model where diverse gliadin peptides may cooperate to promote full cDC2 activation and the subsequent T-cell response in genetically predisposed individuals. SN - 1613-4133 UR - https://www.unboundmedicine.com/medline/citation/31970917/Circulating_Dendritic_Cells_from_Celiac_Disease_Patients_Display_a_Gut-Homing_Profile_and_are_Differentially_Modulated_by_Different_Gliadin-Derived_Peptides L2 - https://doi.org/10.1002/mnfr.201900989 DB - PRIME DP - Unbound Medicine ER -