A Defect in Nucleosome Remodeling Prevents IL-12(p35) Gene Transcription in Neonatal Dendritic Cells

To gain insight into the inability of newborns to mount efficient Th1 responses, we analyzed the molecular basis of defective IL-12(p35) expression in human neonatal monocyte-derived dendritic cells (DCs). Determination of IL-12(p35) pre-mRNA levels by real-time RT-PCR revealed that transcriptional activation of the gene in lipopolysaccharide-stimulated neonatal DCs was strongly impaired compared with adult DCs. We next showed that p50/p65 and p65/p65 dimers interact with kB#1 site, a critical cis-acting element of the IL-12(p35) promoter. We found that LPS-induced p65 activation was similar in adult and newborn DCs. Likewise, in vitro binding activity to the Sp1#1 site, previously shown to be critical for IL-12(p35) gene activation, did not differ in adults and newborns. Since the accessibility to this Sp1#1 site was found to depend on nucleosome remodeling, we used a chromatin accessibility assay to compare remodeling of the relevant nucleosome (nuc-2) in adult and neonatal DCs. We observed that nuc-2 remodeling in neonatal DCs was profoundly impaired in response to lipopolysaccharide. Both nuc-2 remodeling and IL-12(p35) gene transcription were restored upon addition of recombinant interferon-γ. We conclude that IL-12(p35) transcriptional repression in neonatal DCs takes place at the chromatin level

Cardiac myxoma: Related to immunosuppression? A case report

Cardiac myxomas are the most common type of primary cardiac tumours. Nevertheless, it is still a rare tumour and its relation with immunosuppressive therapy, which is essential after organ transplantation, remains uncertain. We report the case of a 30-year-old woman, who underwent kidney and pancreatic transplantation for severe nephropathy due to type I diabetes mellitus and since then, under heavy immunosuppressive treatment. Four years after surgery, a left atrial myxoma was discovered. Three other cases of cardiac myxomas following transplantation and immunodepressive status have been reported in the literature, which raises the question of an association between immunosuppression and the development of cardiac myxomas.SCOPUS: ar.jinfo:eu-repo/semantics/publishe