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Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20
Dendritic cells (DCs) are professional antigen presenting cells involved in the induction of T cell-mediated adaptive immunity. Plasmacytoid DCs (pDCs) originate from lymphoid precursors and produce type I interferons (IFNs) in response to pathogens. A20 is considered as a negative regulator of toll...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756537/ https://www.ncbi.nlm.nih.gov/pubmed/31545817 http://dx.doi.org/10.1371/journal.pone.0222697 |
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author | Duy, Pham Ngoc Thuy, Nguyen Thu Trang, Bui Kieu Giang, Nguyen Hoang Van, Nguyen Thi Hong Xuan, Nguyen Thi |
author_facet | Duy, Pham Ngoc Thuy, Nguyen Thu Trang, Bui Kieu Giang, Nguyen Hoang Van, Nguyen Thi Hong Xuan, Nguyen Thi |
author_sort | Duy, Pham Ngoc |
collection | PubMed |
description | Dendritic cells (DCs) are professional antigen presenting cells involved in the induction of T cell-mediated adaptive immunity. Plasmacytoid DCs (pDCs) originate from lymphoid precursors and produce type I interferons (IFNs) in response to pathogens. A20 is considered as a negative regulator of toll-like receptor (TLR) signaling pathways, in which Toxoplasma gondii- derived profilin (TgPRF) is a TLR11/12 ligand recognised by DCs to stimulate their maturation/activation. Little is known about contributions of A20 to changes in biological properties of pDCs. The present study, therefore, explored whether pDC functions are influenced by A20. To this end, bone marrow cells were isolated and cultured with Flt3L to attain CD8DCs, CD11bDCs and pDCs and followed by challenge with TgPRP in the presence or absence of A20 siRNA. Expression of maturation markers were analysed by flow cytometry, and secretion of inflammatory cytokines by ELISA, cell migration by a transwell migration assay and expression of signalling molecules by western blotting. As a result, treatment with A20 siRNA enhanced activations of IκB-α and STAT-1, leading to increases in expressions of maturation markers and cytokine productions as well as migration of TgPRP-treated pDCs, while mature CD11bDCs produced at higher levels of TNF-α and IL-6 only. In addition, functions of CD8DCs remained unaltered following A20 silencing. The effects of A20 on pDC maturation and activation were completely abolished by IKK inhibitor and partially blunted by fludarabine. In conclusion, the inhibitory effects of A20 on pDC functions are expected to affect the immune response in T. gondii infection. |
format | Online Article Text |
id | pubmed-6756537 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-67565372019-10-04 Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20 Duy, Pham Ngoc Thuy, Nguyen Thu Trang, Bui Kieu Giang, Nguyen Hoang Van, Nguyen Thi Hong Xuan, Nguyen Thi PLoS One Research Article Dendritic cells (DCs) are professional antigen presenting cells involved in the induction of T cell-mediated adaptive immunity. Plasmacytoid DCs (pDCs) originate from lymphoid precursors and produce type I interferons (IFNs) in response to pathogens. A20 is considered as a negative regulator of toll-like receptor (TLR) signaling pathways, in which Toxoplasma gondii- derived profilin (TgPRF) is a TLR11/12 ligand recognised by DCs to stimulate their maturation/activation. Little is known about contributions of A20 to changes in biological properties of pDCs. The present study, therefore, explored whether pDC functions are influenced by A20. To this end, bone marrow cells were isolated and cultured with Flt3L to attain CD8DCs, CD11bDCs and pDCs and followed by challenge with TgPRP in the presence or absence of A20 siRNA. Expression of maturation markers were analysed by flow cytometry, and secretion of inflammatory cytokines by ELISA, cell migration by a transwell migration assay and expression of signalling molecules by western blotting. As a result, treatment with A20 siRNA enhanced activations of IκB-α and STAT-1, leading to increases in expressions of maturation markers and cytokine productions as well as migration of TgPRP-treated pDCs, while mature CD11bDCs produced at higher levels of TNF-α and IL-6 only. In addition, functions of CD8DCs remained unaltered following A20 silencing. The effects of A20 on pDC maturation and activation were completely abolished by IKK inhibitor and partially blunted by fludarabine. In conclusion, the inhibitory effects of A20 on pDC functions are expected to affect the immune response in T. gondii infection. Public Library of Science 2019-09-23 /pmc/articles/PMC6756537/ /pubmed/31545817 http://dx.doi.org/10.1371/journal.pone.0222697 Text en © 2019 Duy et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Duy, Pham Ngoc Thuy, Nguyen Thu Trang, Bui Kieu Giang, Nguyen Hoang Van, Nguyen Thi Hong Xuan, Nguyen Thi Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20 |
title | Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20 |
title_full | Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20 |
title_fullStr | Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20 |
title_full_unstemmed | Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20 |
title_short | Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20 |
title_sort | regulation of nf-κb- and stat1-mediated plasmacytoid dendritic cell functions by a20 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756537/ https://www.ncbi.nlm.nih.gov/pubmed/31545817 http://dx.doi.org/10.1371/journal.pone.0222697 |
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