PMID- 31316504 OWN - NLM STAT- MEDLINE DCOM- 20201021 LR - 20201021 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 10 DP - 2019 TI - Human Oral Epithelial Cells Impair Bacteria-Mediated Maturation of Dendritic Cells and Render T Cells Unresponsive to Stimulation. PG - 1434 LID - 10.3389/fimmu.2019.01434 [doi] LID - 1434 AB - The oral mucosa is a first line of defense against pathogenic organisms and yet tolerates food antigens and resident bacteria. Mucosal epithelial cells are emerging as important regulators of innate and adaptive immune responses. However, the contribution of oral epithelial cells (OECs) determining oral immunity is understudied. Here, we evaluated the ability of H413 and TR146 cells, two OEC lines derived from human oral squamous cell carcinomas, and primary OECs to modulate immune responses to a cocktail of Gram(+) and Gram(-) bacteria known as MV130. OECs expressed CD40 constitutively and class II major histocompatibility complex (MHC II) molecules when stimulated with IFNgamma, but not CD80 or CD86. Dendritic cells (DCs) treated with bacteria in co-culture with OECs did not fully mature, as judged by the expression of MHC II, CD80 and CD86, and barely released IL-12 and TNFalpha, compared to control DCs. Furthermore, in the presence of OECs, DCs were unable to stimulate allogenic naive CD4 T cells to produce IFNgamma and TNFalpha. Similarly, OECs in culture with total CD4 T cells or Th1 cells stimulated with anti-CD3 and anti-CD28 antibodies abrogated CD25 and CD69 expression, T cell proliferation and the release of IFNgamma and TNFalpha. The inhibition on T cell activation by OECs was cell-contact dependent, TGFbeta independent and largely irreversible. Overall, this behavior of OECs is likely key to avoid immune system over-reaction against resident bacteria. FAU - Molero-Abraham, Magdalena AU - Molero-Abraham M AD - Department of Immunology, School of Medicine, Complutense University of Madrid, Madrid, Spain. FAU - Sanchez-Trincado, Jose L AU - Sanchez-Trincado JL AD - Department of Immunology, School of Medicine, Complutense University of Madrid, Madrid, Spain. FAU - Gomez-Perosanz, Marta AU - Gomez-Perosanz M AD - Department of Immunology, School of Medicine, Complutense University of Madrid, Madrid, Spain. FAU - Torres-Gomez, Alvaro AU - Torres-Gomez A AD - Department of Immunology, School of Medicine, Complutense University of Madrid, Madrid, Spain. FAU - Subiza, Jose Luis AU - Subiza JL AD - Inmunotek SL, Madrid, Spain. FAU - Lafuente, Esther M AU - Lafuente EM AD - Department of Immunology, School of Medicine, Complutense University of Madrid, Madrid, Spain. FAU - Reche, Pedro A AU - Reche PA AD - Department of Immunology, School of Medicine, Complutense University of Madrid, Madrid, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190628 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Cytokines) SB - IM MH - CD4-Positive T-Lymphocytes/immunology MH - Cell Line, Tumor MH - Cell Proliferation MH - Cytokines/immunology MH - Dendritic Cells/*immunology MH - Epithelial Cells/*immunology/*microbiology MH - *Gram-Negative Bacteria MH - *Gram-Positive Bacteria MH - Humans MH - Mouth Mucosa/*cytology/immunology PMC - PMC6611079 OTO - NOTNLM OT - T cells OT - bacteria OT - dendritic cells OT - immunomodulation OT - oral epithelial cells EDAT- 2019/07/19 06:00 MHDA- 2020/10/22 06:00 PMCR- 2019/01/01 CRDT- 2019/07/19 06:00 PHST- 2019/03/22 00:00 [received] PHST- 2019/06/07 00:00 [accepted] PHST- 2019/07/19 06:00 [entrez] PHST- 2019/07/19 06:00 [pubmed] PHST- 2020/10/22 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2019.01434 [doi] PST - epublish SO - Front Immunol. 2019 Jun 28;10:1434. doi: 10.3389/fimmu.2019.01434. eCollection 2019.