Correlation between miR-126 expression and DNA hypomethylation of CD4+T cells in rheumatoid arthritis patients
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
Authors: Yang, Ge; Wu, Daoquan; Zeng, Guang; Jiang, Ou; Yuan, Pingzong; Huang, Shenjie; Zhu, Jing; Tian, Jie; Weng, Yaguang; Rao, Zhihua
Abstract
It has been known that the occurrence of rheumatoid arthritis (RA) was closely correlated with DNA hypomethylation in CD4+ T cells, in which DNA methyltransferase plays a certain role. This study therefore investigated the effect of miR-126 on CD4+ T cell subgroup in RA patients and the alternation of DNA hypomethylation, in an attempt to provide new sights into the pathogenesis and treatment of RA. CD4+ T cells separated from RA patients were transfected with miRNA (miR)-126 expression vector or miR-126 inhibitor expression vector. The expression levels of CD11a, CD70 and DNMT1 mRNA were examined by real-time PCR. Protein levels of CD11a and CD70 were tested by flow cytometry while DNMT1 protein level was quantified by Western blotting. DNA was modified by sodium bisulfite and was sequenced for the methylation status of promoters of CD11a and CD70 genes. Both mRNA and protein expressions of CD11a and CD70 genes in CD4+ T cells were elevated by miR-126 transfection, along with decreased DNMT1 protein level but not mRNA level. The methylation degree of promoters of both CD11a and CD70 genes were significantly depressed after miR-126 transfection. The transfection by miR-126 inhibitor effectively reversed such effects. In RA patients, elevated miR-126 may promote the expression of CD11a and CD70 via the induction of hypomethylation of gene promoters by depressing DNMTI1 protein levels.
Maturation and migration of dendritic cells upon stimulation with heat-killed tumor cells
ANIMAL CELLS AND SYSTEMS
Authors: Kim, Hyojeong; Yoon, Taek Joon; Lee, Sung Won; Yun, Daesun; Kim, Ji Yeon; Shin, Kwang-Soon; Park, Se-Ho; Hong, Seokmann
Abstract
Recently it has been reported that immunization with heat-killed tumor cells (HK vaccine) induces anti-tumor immune responses in mice. To investigate how HK vaccine elicits anti-tumor specific adaptive immunity, we examined the effect of HK vaccination on innate immune cells such as dendritic cells (DCs), which are essential for the generation of adaptive immunity. Upon stimulation with HK vaccine, DCs matured to promote not only the up-regulation of co-stimulatory molecules but also secretion of cytokine IL12. Furthermore, HK vaccine-treated DCs migrated more efficiently to draining lymph nodes compared with untreated ones. Taken together, HK vaccine can be useful as an adjuvant to activate DCs for anti-tumor immune responses.