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...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2019-01-01
|
Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0222697 |
id |
doaj-e5267577855a4fcea6be5d4ca987e2dc |
---|---|
record_format |
Article |
spelling |
doaj-e5267577855a4fcea6be5d4ca987e2dc2021-03-03T21:07:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01149e022269710.1371/journal.pone.0222697Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20.Pham Ngoc DuyNguyen Thu ThuyBui Kieu TrangNguyen Hoang GiangNguyen Thi Hong VanNguyen Thi XuanDendritic 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.https://doi.org/10.1371/journal.pone.0222697 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pham Ngoc Duy Nguyen Thu Thuy Bui Kieu Trang Nguyen Hoang Giang Nguyen Thi Hong Van Nguyen Thi Xuan |
spellingShingle |
Pham Ngoc Duy Nguyen Thu Thuy Bui Kieu Trang Nguyen Hoang Giang Nguyen Thi Hong Van Nguyen Thi Xuan Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20. PLoS ONE |
author_facet |
Pham Ngoc Duy Nguyen Thu Thuy Bui Kieu Trang Nguyen Hoang Giang Nguyen Thi Hong Van Nguyen Thi Xuan |
author_sort |
Pham Ngoc Duy |
title |
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_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_sort |
regulation of nf-κb- and stat1-mediated plasmacytoid dendritic cell functions by a20. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
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. |
url |
https://doi.org/10.1371/journal.pone.0222697 |
work_keys_str_mv |
AT phamngocduy regulationofnfkbandstat1mediatedplasmacytoiddendriticcellfunctionsbya20 AT nguyenthuthuy regulationofnfkbandstat1mediatedplasmacytoiddendriticcellfunctionsbya20 AT buikieutrang regulationofnfkbandstat1mediatedplasmacytoiddendriticcellfunctionsbya20 AT nguyenhoanggiang regulationofnfkbandstat1mediatedplasmacytoiddendriticcellfunctionsbya20 AT nguyenthihongvan regulationofnfkbandstat1mediatedplasmacytoiddendriticcellfunctionsbya20 AT nguyenthixuan regulationofnfkbandstat1mediatedplasmacytoiddendriticcellfunctionsbya20 |
_version_ |
1714818730953801728 |