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.

Chronic myeloid leukemia (CML) is a blood cancer involved in abnormal proliferation of myeloid cells at all stages of differentiation. Translocation of regions of the BCR and ABL genes, leading to the fusion gene BCR-ABL, which forms the Philadelphia (Ph) chromosome, is the cause of more than 90% of CML. The BCR-ABL protein shows abnormal tyrosine kinase activity, leading to changes in proliferation signals including signal transducer and activator of transcriptions (STATs) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and resulting in uncontrolled proliferation of myeloid cells. CTLA-4, PD-1 and LAG3 genes are known as immunosuppressive receptors playing important roles in controlling immune response by inhibiting activity of T helper cells. Klotho gene has anti-aging, anti-inflammatory and anti-cancer functions. STAT signaling pathway genes regulate cancer cell functions by their phosphorylation and IκB-α gene by degradation of its expression. In this study, we conducted experiments to determine mRNA expression of these genes on immune cells in CML patients by using realtime-PCR. Results showed a marked increase in the expression of STAT-1 and STAT-6 signaling genes and a decreased LAG3 expression in CML patients as compared with healthy controls. In addition, other gene expressions such as CTLA4, PD1, klotho, IκB-α, STAT3 and STAT5 were unaltered in CML cells. The abnormal increased expression of STAT1 and STAT6 genes indicated an important role of these signaling genes in regulating activity of immune cells, leading to pathogenesis and development of CML disease. The evidence suggested that STAT-1 and STAT-6 genes could be important and potential markers in early prognosis of CML.