Type 1 diabetes: defective protection against attack on the body's own cells

miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes. Nature Communications, 2019

Source: Carolin Daniel, Helmholtz Zentrum München

 

Regulatory T cells (Tregs) prevent excessive immune reactions in healthy people. In the development of autoimmune type 1 diabetes, this protection is not sufficiently effective. Researchers at the DZD have now deciphered a mechanism that impairs Treg differentiation and stability. The results have now been published in 'Nature Communications'.

Prof. Dr. Carolin Daniel's team was able to decipher a mechanism that leads to the formation of less functional Tregs at an early stage of type 1 diabetes. The microRNA 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 Carolin Daniel. 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.

New target for future intervention strategies

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.

Researchers at the Institute of Diabetes Research (IDF) of Helmholtz Zentrum München, the German Center for Diabetes Research (DZD) and Ludwig-Maximilians-Universität Munich were involved in the studies.

Original publication: 
Scherm, M. G. et al. (2019):  miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes. Nature Communications, DOI: 10.1038/s41467-019-13587-3