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Human Oral Epithelial Cells Suppress T Cell Function via Prostaglandin E2 Secretion

The oral mucosa is constantly exposed to a plethora of stimuli including food antigens, commensal microbiota and pathogens, requiring distinct immune responses. We previously reported that human oral epithelial cells (OECs) suppress immune responses to bacteria, using H413 and TR146 OEC lines and pr...

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Autores principales: Sanchez-Trincado, Jose L., Pelaez-Prestel, Hector F., Lafuente, Esther M., Reche, Pedro A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807503/
https://www.ncbi.nlm.nih.gov/pubmed/35126344
http://dx.doi.org/10.3389/fimmu.2021.740613
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author Sanchez-Trincado, Jose L.
Pelaez-Prestel, Hector F.
Lafuente, Esther M.
Reche, Pedro A.
author_facet Sanchez-Trincado, Jose L.
Pelaez-Prestel, Hector F.
Lafuente, Esther M.
Reche, Pedro A.
author_sort Sanchez-Trincado, Jose L.
collection PubMed
description The oral mucosa is constantly exposed to a plethora of stimuli including food antigens, commensal microbiota and pathogens, requiring distinct immune responses. We previously reported that human oral epithelial cells (OECs) suppress immune responses to bacteria, using H413 and TR146 OEC lines and primary OECs in co-culture with dendritic cells (DCs) and T cells (OEC-conditioned cells). OECs reduced DCs expression of CD80/CD86 and IL-12/TNFα release and impaired T cell activation. Here, we further evaluated the immunosuppression by these OECs and investigated the underlying mechanisms. OEC-conditioned DCs did not induce CD4 T cell polarization towards Treg, judging by the absence of FoxP3 expression. OECs also repressed T-bet/IFNγ expression in CD4 and CD8 T cells activated by DCs or anti-CD3/CD28 antibodies. This inhibition depended on OEC:T cell ratio and IFNγ repression occurred at the transcriptional level. Time-lapse experiments showed that OECs inhibited early steps of T cell activation, consistent with OECs inability to suppress T cells stimulated with PMA/ionomycin. Blocking CD40/CD40L, CD58/CD2 and PD-L1/PD-1 interactions with specific antibodies did not disrupt T cell suppression by OECs. However, preventing prostaglandin E2 (PGE2) synthesis or blocking PGE2 binding to the cognate EP2/EP4 receptors, restored IFNγ and TNFα production in OEC-conditioned T cells. Finally, treating OECs with poly(I:C), which simulates viral infections, limited T cell suppression. Overall, these results point to an inherent ability of OECs to suppress immune responses, which can nonetheless be eluded when OECs are under direct assault.
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spelling pubmed-88075032022-02-03 Human Oral Epithelial Cells Suppress T Cell Function via Prostaglandin E2 Secretion Sanchez-Trincado, Jose L. Pelaez-Prestel, Hector F. Lafuente, Esther M. Reche, Pedro A. Front Immunol Immunology The oral mucosa is constantly exposed to a plethora of stimuli including food antigens, commensal microbiota and pathogens, requiring distinct immune responses. We previously reported that human oral epithelial cells (OECs) suppress immune responses to bacteria, using H413 and TR146 OEC lines and primary OECs in co-culture with dendritic cells (DCs) and T cells (OEC-conditioned cells). OECs reduced DCs expression of CD80/CD86 and IL-12/TNFα release and impaired T cell activation. Here, we further evaluated the immunosuppression by these OECs and investigated the underlying mechanisms. OEC-conditioned DCs did not induce CD4 T cell polarization towards Treg, judging by the absence of FoxP3 expression. OECs also repressed T-bet/IFNγ expression in CD4 and CD8 T cells activated by DCs or anti-CD3/CD28 antibodies. This inhibition depended on OEC:T cell ratio and IFNγ repression occurred at the transcriptional level. Time-lapse experiments showed that OECs inhibited early steps of T cell activation, consistent with OECs inability to suppress T cells stimulated with PMA/ionomycin. Blocking CD40/CD40L, CD58/CD2 and PD-L1/PD-1 interactions with specific antibodies did not disrupt T cell suppression by OECs. However, preventing prostaglandin E2 (PGE2) synthesis or blocking PGE2 binding to the cognate EP2/EP4 receptors, restored IFNγ and TNFα production in OEC-conditioned T cells. Finally, treating OECs with poly(I:C), which simulates viral infections, limited T cell suppression. Overall, these results point to an inherent ability of OECs to suppress immune responses, which can nonetheless be eluded when OECs are under direct assault. Frontiers Media S.A. 2022-01-19 /pmc/articles/PMC8807503/ /pubmed/35126344 http://dx.doi.org/10.3389/fimmu.2021.740613 Text en Copyright © 2022 Sanchez-Trincado, Pelaez-Prestel, Lafuente and Reche https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Sanchez-Trincado, Jose L.
Pelaez-Prestel, Hector F.
Lafuente, Esther M.
Reche, Pedro A.
Human Oral Epithelial Cells Suppress T Cell Function via Prostaglandin E2 Secretion
title Human Oral Epithelial Cells Suppress T Cell Function via Prostaglandin E2 Secretion
title_full Human Oral Epithelial Cells Suppress T Cell Function via Prostaglandin E2 Secretion
title_fullStr Human Oral Epithelial Cells Suppress T Cell Function via Prostaglandin E2 Secretion
title_full_unstemmed Human Oral Epithelial Cells Suppress T Cell Function via Prostaglandin E2 Secretion
title_short Human Oral Epithelial Cells Suppress T Cell Function via Prostaglandin E2 Secretion
title_sort human oral epithelial cells suppress t cell function via prostaglandin e2 secretion
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807503/
https://www.ncbi.nlm.nih.gov/pubmed/35126344
http://dx.doi.org/10.3389/fimmu.2021.740613
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