Sjögren syndrome is a rare disease, occurring in roughly 1 of 10,000 adults, usually after the age of 50. It causes inflammation in exocrine glands, particularly those of the eyes and mouth. These glands become infiltrated with B and T lymphocytes and cease excreting sufficient fluid to the skin or membranes.
MicroRNAs are small bits of RNA that regulate gene expression post-transcriptionally: they bind to messenger RNA to inhibit the translation of these latter into proteins. MicroRNAs are thus epigenetic agents, that is, they modify gene expression without modifying gene sequence. The CNRGH team headed by Jörg Tost performed a quantitative study on the microRNA expressed in the B and T lymphocytes of patients with Sjögren syndrome compared to those of patients without the disorder. Unprecedentedly, they were able to demonstrate that patients with Sjögren syndrome expressed microRNAs differently than control patients did and in different ways for each cell type.
To study the impact of this dysregulation, they team focused on a specific, downregulated microRNA: miR-30b-5p. This latter targets the messenger RNA for B-cell activating factor (BAFF), which plays a key role in the development of Sjögren syndrome. Indeed, when the authors used a synthetic microRNA inhibitor (an antagomir) to block miR-30b-5p, they observed an increase in BAFF expression. Their results suggest the possibility of a treatment for Sjögren syndrome based on the administration of microRNA in the glands where they are underexpressed. Such an approach may be able to control the activation of the lymphocytes responsible for the disease.
1 National Center of Human Genomics Research, Epigenetic and Environment
Laboratory.
2 Epigenetic mechanisms modify the expression (the function) of genes
without changing their DNA sequence. These mechanisms include methylation and
phosphorylation of histones or DNA, and the actions of microRNAs, among others.