TET2 Modulates Neural Immune Response

A paper published today in Cell Reports reveals new findings about the mechanisms that regulate brain inflammation. The findings open a new path of study in the field of neuroinflammation. In neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases—for which there is still no effective treatment—it is believed that neural immune cells (microglia) play a key role in pathology and progression; therefore, discovery of new mechanisms regulating microglial function could lead to the discovery of new therapeutic targets to use in clinic.

The authors found that a protein called TET2 is responsible for modulating the immune response generated in the microglia in the brain under inflammatory conditions. The authors observe that, in transgenic mice lacking TET2 in their microglia cells, the neuroinflammatory response is hampered in a neuroinflammatory model. Normally TET2, together with other proteins, regulates the activity of genes by removing certain chemical marks from DNA, but the authors found that this mechanism was not behind the role of TET2 in microglia.

“TET2 appears to act in microglia by a different mechanism to that seen in other cells that mediate inflammation outside of the brain,” says coauthor Miguel Branco of Queen Mary University of London.

“We observe that microglia cells in a proinflammatory environment increase the expression of TET2, and this protein becomes a key regulator for many of the changes that leads to the full activation of these cells,” adds coauthor Miguel Burguillos of the University of Seville.

Although this is an exploratory study, the new mechanism described in this paper opens a new route of study for the research of mechanisms governing microglia under disease conditions. Thus, TET2 could become a significant component for different neurodegenerative diseases—such as Parkinson’s disease and Alzheimer’s disease—in which neuroinflammation driven by microglia contributes to pathology.