Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20


Autoři: Pham Ngoc Duy aff001;  Nguyen Thu Thuy aff002;  Bui Kieu Trang aff003;  Nguyen Hoang Giang aff003;  Nguyen Thi Hong Van aff004;  Nguyen Thi Xuan aff003
Působiště autorů: Faculty of Biotechnology, Vietnam National University of Agriculture, Trau Quy, Gia Lam, Hanoi, Vietnam aff001;  Institute of Biomedicine and Pharmacy, Vietnam Military Medical University, Ha Dong, Hanoi, Vietnam aff002;  Institute of Genome Research, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam aff003;  Department of Genetics, Faculty of Biology, VNU University of Science, Thanh Xuan, Hanoi, Vietnam aff004;  Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Cau Giay, Ha Noi, Vietnam aff005
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222697

Souhrn

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.

Klíčová slova:

Cell migration – Cytokines – Secretion – Signal inhibition – Small interfering RNAs – Toxoplasma gondii – Toll-like receptors – Arithmetic


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