Type 1 diabetes is the most common metabolic disease in children and adolescents. In this autoimmune disease, the body's own immune cells gradually destroy the insulin-producing beta cells in the pancreas. Normally, regulatory T cells (Tregs) prevent an attack on the body's own cells. However, during the development of type 1 diabetes, this protection is insufficient. The team has now deciphered a molecular mechanism that during an early phase of type 1 diabetes leads to the formation of decreased numbers of functional Tregs.

Elevated levels of miRNA142-3p contribute to the development and progression of autoimmunity. The miRNA142-3p plays a decisive role in this process. MicroRNAs can suppress the expression of individual genes. "During the development of autoimmunity in type 1 diabetes, we were able to detect an increased abundance of miRNA142-3p. This leads to a reduced expression of the protein Tet2 in T-helper cells," said first author. As a consequence, faulty epigenetic changes occur in the Foxp3 gene of the regulatory T cells. A decreased number of these important immune cells are formed, and the Tregs are no longer as stable.

"Our research results show a direct link between miRNA142-3p and the impaired function of regulatory T cells, which subsequently contributes to the development and progression of autoimmunity," said last author summarizing the results of the this study.

In order to investigate whether the findings could also open up new therapeutic approaches in the future, the scientists specifically blocked the miRNA142-3p molecule. This improved the formation and stability of the regulatory T cells. In the animal model, the autoimmune response to the insulin-producing beta cells also decreased.

The researchers have plans for follow-up studies: In order to further investigate the potential of the targeted inhibition of specific miRNAs, the next step will be to improve the selective and targeted accumulation of the miRNA142-3p inhibitor in the relevant target cells. The researchers are already making plans: In addition, Carolin Daniel's team also wants to identify further genes that are regulated by miRNA142-3p and/or Tet2 and whose dysregulation can contribute to the development and progression of islet autoimmunity.

https://www.dzd-ev.de/en/press/press-releases/press-releases-2019/type-1-diabetes-researchers-identify-new-molecular-target-to-prevent-progression-of-islet-autoimmunity/index.html

https://www.nature.com/articles/s41467-019-13587-3

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fmirna142-3p-targets&filter=22