Researchers detected the expression of the gene ANKRD55 in immune cells, a gene that has been previously linked to multiple sclerosis (MS) in mice models of the disease. The results suggest a potential role of ANKRD55 in MS pathogenesis. The study, “Novel Insights into the Multiple Sclerosis Risk Gene ANKRD55,” was published in The Journal of Immunology.
The team of scientists at The Neurogenomiks research group, linked to the Achucarro Basque Centre for Neuroscience (EHU group) and the University of the Basque Country (UPV/EHU) investigated the gene known as ANKRD55. A genetic variant of the ANKRD55 gene, identified as rs6859219, was previously reported to be a genetic risk factor for MS. However, the biological mechanisms associated with this link remain poorly characterized.
Researchers studied ANKRD55 expression in human peripheral blood mononuclear cells (PBMCs), populations of immune cells present in the blood, and other cell lines. They detected three ANKRD55 transcript variants specifically in PBMCs and CD4+ T cells, a special category of immune cells. In contrast, ANKRD55 transcript variants were absent of CD8+, CD14+, CD19+, and CD56+ cells. The particular genetic variant linked to MS was associated with an increased expression of all three ANKRD55 transcripts. This increase was predominant in the CD4+ T cells, where it was located into the cells’ nucleus.
The results suggest that ANKRD55 has a potential significant biological function in these cells, a phenomenon researchers point out needs to be addressed in future studies. In MS, CD4+ T cells are deregulated, and these new findings suggest that ANKRD55 may be involved in this deregulation.
Since ANKRD55 proteins were located in the nuclei of the cells, they could regulate specific programs, such as gene transcription. In murine hippocampal neurons and microglia, as well as in a murine mouse model of experimental autoimmune encephalomyelitis (the most commonly used experimental model for human MS), the researchers found an increase in ANKRD55 protein expression. Additionally, central nervous system-infiltrating mononuclear cells in this mice model showed that CD4+ T cells and monocytes express the ANKRD55 protein.
Future studies investigating the functions of ANKRD55 transcripts and their role in MS may lead to novel diagnostic and therapeutic approaches for MS patients, the researchers concluded.
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