23 research outputs found
Immunoproteasome LMP2 60HH Variant Alters MBP Epitope Generation and Reduces the Risk to Develop Multiple Sclerosis in Italian Female Population
Background: Albeit several studies pointed out the pivotal role that CD4+T cells have in Multiple Sclerosis, the CD8+ T cells
involvement in the pathology is still in its early phases of investigation. Proteasome degradation is the key step in the
production of MHC class I-restricted epitopes and therefore its activity could be an important element in the activation and
regulation of autoreactive CD8+ T cells in Multiple Sclerosis.
Methodology/Principal Findings: Immunoproteasomes and PA28-ab regulator are present in MS affected brain area and
accumulated in plaques. They are expressed in cell types supposed to be involved in MS development such as neurons,
endothelial cells, oligodendrocytes, macrophages/macroglia and lymphocytes. Furthermore, in a genetic study on 1262
Italian MS cases and 845 controls we observed that HLA-A*02+ female subjects carrying the immunoproteasome LMP2
codon 60HH variant have a reduced risk to develop MS. Accordingly, immunoproteasomes carrying the LMP2 60H allele
produce in vitro a lower amount of the HLA-A*0201 restricted immunodominant epitope MBP111\u2013119.
Conclusion/Significance: The immunoproteasome LMP2 60HH variant reduces the risk to develop MS amongst Italian HLAA*
02+ females. We propose that such an effect is mediated by the altered proteasome-dependent production of a specific
MBP epitope presented on the MHC class I. Our observations thereby support the hypothesis of an involvement of
immunoproteasome in the MS pathogenesis
Long‐Term Results of Cultured Limbal Stem Cell Versus Limbal Tissue Transplantation in Stage III Limbal Deficiency
Lower Serum Levels of Th2-Related Chemokine CCL22 in Women Patients with Multiple Sclerosis: A Comparison Between Patients and Healthy Women
NEDDylation antagonizes ubiquitination of proliferating cell nuclear antigen and regulates the recruitment of polymerase η in response to oxidative DNA damage
Structure analysis of FAAP24 reveals single-stranded DNA-binding activity and domain functions in DNA damage response
The Role of Kinin Receptors in Preventing Neuroinflammation and Its Clinical Severity during Experimental Autoimmune Encephalomyelitis in Mice
Chromatin structure and the inheritance of epigenetic information
Although it is widely accepted that the regulation of the chromatin landscape is pivotal to conveying epigenetic phenomena, it is still unclear how a defined chromatin domain is reproduced following replication and transmitted from one generation to another. Here we review multiple mechanisms that contribute to the inheritance of epigenetic information with emphasis on the recycling of old histones following replication, the requirement for a positive feedback loop, long-range gene interactions, and the complex network of trans-acting factors