Celiac Disease Causes Epithelial Disruption and Regulatory T Cell Recruitment in the Oral Mucosa
Celiac disease (CD) is a chronic autoimmune disease characterized by an immune-triggered enteropathy upon gluten intake. The only current treatment available is lifelong Gluten Free Diet (GFD). Several extraintestinal manifestations have been described in CD, some affecting the oral mucosa. Thus, we...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.623805/full |
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| author | Javier Sanchez-Solares Luis Sanchez Carmela Pablo-Torres Celso Diaz-Fernandez Poul Sørensen Poul Sørensen Domingo Barber Domingo Barber Cristina Gomez-Casado Cristina Gomez-Casado |
| author_facet | Javier Sanchez-Solares Luis Sanchez Carmela Pablo-Torres Celso Diaz-Fernandez Poul Sørensen Poul Sørensen Domingo Barber Domingo Barber Cristina Gomez-Casado Cristina Gomez-Casado |
| author_sort | Javier Sanchez-Solares |
| collection | DOAJ |
| description | Celiac disease (CD) is a chronic autoimmune disease characterized by an immune-triggered enteropathy upon gluten intake. The only current treatment available is lifelong Gluten Free Diet (GFD). Several extraintestinal manifestations have been described in CD, some affecting the oral mucosa. Thus, we hypothesized that oral mucosa could potentially be a target for novel biomarkers and an administration route for CD treatment. Six de novo diagnosed and seven CD patients under GFD for at least 1 year were recruited. Non-celiac subjects (n = 8) were recruited as control group. Two biopsies of the cheek lining were taken from each subject for mRNA analysis and immunohistochemical characterization. We observed a significant decrease in the expression of epithelial junction proteins in all CD patients, indicating that oral mucosa barrier integrity is compromised. FoxP3+ population was greatly increased in CD patients, suggesting that Tregs are recruited to the damaged mucosa, even after avoidance of gluten. Amphiregulin mRNA levels from Peripheral Blood Mononuclear Cells (PBMCs) and epithelial damage in the oral mucosa correlated with Treg infiltration in all the experimental groups, suggesting that recruited Tregs might display a “repair” phenotype. Based on these results, we propose that oral mucosa is altered in CD and, as such, might have diagnostic potential. Furthermore, due to its tolerogenic nature, it could be an important target for oral immunotherapy. |
| first_indexed | 2024-12-13T12:31:25Z |
| format | Article |
| id | doaj.art-62fbc4e3af534ca7be6a86802df82fff |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T12:31:25Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-62fbc4e3af534ca7be6a86802df82fff2022-12-21T23:46:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011210.3389/fimmu.2021.623805623805Celiac Disease Causes Epithelial Disruption and Regulatory T Cell Recruitment in the Oral MucosaJavier Sanchez-Solares0Luis Sanchez1Carmela Pablo-Torres2Celso Diaz-Fernandez3Poul Sørensen4Poul Sørensen5Domingo Barber6Domingo Barber7Cristina Gomez-Casado8Cristina Gomez-Casado9Institute of Applied Molecular Medicine, Hospitals Madrid (HM) Group, San Pablo-CEU University, Madrid, SpainService of Gastroenterology, University Hospital San Agustin (HUSA), Aviles, SpainInstitute of Applied Molecular Medicine, Hospitals Madrid (HM) Group, San Pablo-CEU University, Madrid, SpainDepartment of Otolaryngology Head and Neck Surgery, University Hospital San Agustin (HUSA), Aviels, SpainAllero Therapeutics BV, Rotterdam, NetherlandsDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkInstitute of Applied Molecular Medicine, Hospitals Madrid (HM) Group, San Pablo-CEU University, Madrid, SpainARADyAL-RD16/0006/0015, Thematic Network and Cooperative Research Centers, ISCIII, Madrid, SpainInstitute of Applied Molecular Medicine, Hospitals Madrid (HM) Group, San Pablo-CEU University, Madrid, SpainARADyAL-RD16/0006/0015, Thematic Network and Cooperative Research Centers, ISCIII, Madrid, SpainCeliac disease (CD) is a chronic autoimmune disease characterized by an immune-triggered enteropathy upon gluten intake. The only current treatment available is lifelong Gluten Free Diet (GFD). Several extraintestinal manifestations have been described in CD, some affecting the oral mucosa. Thus, we hypothesized that oral mucosa could potentially be a target for novel biomarkers and an administration route for CD treatment. Six de novo diagnosed and seven CD patients under GFD for at least 1 year were recruited. Non-celiac subjects (n = 8) were recruited as control group. Two biopsies of the cheek lining were taken from each subject for mRNA analysis and immunohistochemical characterization. We observed a significant decrease in the expression of epithelial junction proteins in all CD patients, indicating that oral mucosa barrier integrity is compromised. FoxP3+ population was greatly increased in CD patients, suggesting that Tregs are recruited to the damaged mucosa, even after avoidance of gluten. Amphiregulin mRNA levels from Peripheral Blood Mononuclear Cells (PBMCs) and epithelial damage in the oral mucosa correlated with Treg infiltration in all the experimental groups, suggesting that recruited Tregs might display a “repair” phenotype. Based on these results, we propose that oral mucosa is altered in CD and, as such, might have diagnostic potential. Furthermore, due to its tolerogenic nature, it could be an important target for oral immunotherapy.https://www.frontiersin.org/articles/10.3389/fimmu.2021.623805/fullceliac diseaseoral mucosaremodelingregulatory T cellsimmunotherapytolerance induction |
| spellingShingle | Javier Sanchez-Solares Luis Sanchez Carmela Pablo-Torres Celso Diaz-Fernandez Poul Sørensen Poul Sørensen Domingo Barber Domingo Barber Cristina Gomez-Casado Cristina Gomez-Casado Celiac Disease Causes Epithelial Disruption and Regulatory T Cell Recruitment in the Oral Mucosa Frontiers in Immunology celiac disease oral mucosa remodeling regulatory T cells immunotherapy tolerance induction |
| title | Celiac Disease Causes Epithelial Disruption and Regulatory T Cell Recruitment in the Oral Mucosa |
| title_full | Celiac Disease Causes Epithelial Disruption and Regulatory T Cell Recruitment in the Oral Mucosa |
| title_fullStr | Celiac Disease Causes Epithelial Disruption and Regulatory T Cell Recruitment in the Oral Mucosa |
| title_full_unstemmed | Celiac Disease Causes Epithelial Disruption and Regulatory T Cell Recruitment in the Oral Mucosa |
| title_short | Celiac Disease Causes Epithelial Disruption and Regulatory T Cell Recruitment in the Oral Mucosa |
| title_sort | celiac disease causes epithelial disruption and regulatory t cell recruitment in the oral mucosa |
| topic | celiac disease oral mucosa remodeling regulatory T cells immunotherapy tolerance induction |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.623805/full |
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