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.
Acute promyelocytic leukemia (APL) is a type of acute leukemia, which has the highest death rate among blood cancers and caused by a specific (15; 17) chromosomal translocation, resulting in a fusion gene PML/RARα. Klotho gene plays a role in preventing aging, inflammation and cancer. CTLA4, PD1 and LAG3 are immunosuppressive receptors located on surface of T cells and considered as a negative regulation of immune response. These genes regulate immune cell activity through several signalling moleculars such as STATs and NF-κB. In this study, to additionally determine the difference between APL and other leukemia, we performed experiments to measure mRNA expression of above genes by using realtime-PCR. Results showed that mRNA levels of KL, CTLA4, PD1 and LAG3 genes were lower, while expressions of STAT1, STAT3, STAT5 and STAT6 genes were significantly higher in APL patients than healthy controls. In addition, IκB-α gene expression was unaltered on APL cells. 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Psoriasis is a chronic autoimmune disease characterized by abnormal proliferation and differentiation of keratinocytes and infiltration of inflammatory cells into the site of inflammation. Plaque psoriasis is the most common type of psoriasis, affecting up to 80–90% of psoriasis cases. Among inflammatory cells, myeloid dendritic cells or Langerhans cells are mainly activated cells during the pathogenesis of psoriasis to induce activation and differentiation of naive T cells into T helper cells (Th)1 and Th17 cells. SH2 domain-containing protein tyrosine phosphatase (SHP) is a negative regulator of the phosphorylation of several proteins involved in cellular differentiation, growth and activation. Chronic inflammation promotes tumor progression, which is characterized by the release of carcinogenic antigens, including alpha-fetoprotein (AFP) and cancer antigen 125 (CA125) into blood and urine. They are common tumor markers to serve as predictors of cancer development and survival of cancer patients. To this end, blood samples of 103 psoriasis patients and 46 healthy subjects were collected. The mRNA expressions of SHP1 and SHP2 were examined by using quantitative RT-PCR and the serum levels of IL-6, TNF-α, IFN-γ, IL-17A, AFP and CA125 by ELISA. As a result, the mRNA level of SHP1 was higher expressed, whereas the level of SHP2 was unaltered in the patient group compared to the control individuals. Importantly, psoriasis patients had CA125 level higher than the clinical cutoff 35U/mL was 15.6%, while healthy individuals had CA125 level lower than 35U/mL. In addition, the serum TNF-α and IL-17A concentrations were significantly increased in the patient group. In conclusion, the results indicated the significant differences in expression of SHP1 gene and inflammatory response in psoriasis patients. This study further hint for investigations on the functional role of SHP1 in regulating activation of immune cells present in psoriasis patients.
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