Nat Immunol: Key gene regulates immune system 'brake'

Oct 3, 2020 /--- Unlike most T-cells, which initiate an immune response to foreign molecules, regulatory T-cells are peaceful messengers of the human immune system and suppress inflammatory responses when not needed.
now, researchers at the Gladstone Institute, in collaboration with scientists at the University of California, San Francisco (UCSF) and the University of Technology Munich (TUM), have mapped out a genetic network that helps distinguish regulatory T cells from other T cells.
their findings may lead to immunotherapy that enhances or impairs the function of regulatory T-cells.
The integration of the genetic networks of regulatory T-cell biology is the first step in finding drug targets that can alter these cell functions to treat cancer and autoimmune diseases," said Alex Marson, director of the Gladstone-UCSF Institute for Genetic Immunology.
(Photo: www.pixabay.com) All T-cells mature in the thymus, have similar properties on their surfaces, and play a role in disrupting the immune response of viruses, bacteria and certain cancer cells.
but regulatory T-cells have a unique function that inhibits other T-cells so that the immune response does not overreact.
mice have shown that increasing the number of regulated T-cells, which put a stronger "brake" on the immune system, may help alleviate the symptoms of autoimmune diseases.
, on the other hand, blocking regulatory T cells or lifting the brakes on these molecules helps the immune system better fight cancer.
therapy to increase the number of regulated T-cells by removing cells from patients, amplification of cells, and then injecting them into cells has been tested in patients with autoimmune diseases, including type 1 diabetes, and in recipients of organ transplants.
, however, so far, such treatments have generally not involved actually altering the function of immune cells.
"Most of our previous knowledge about regulatory T cells came from mouse models," said lead author Kathrin Schumann.
once we understand the function of each gene, we can precisely edit cells to treat disease.
study, published in the journal Nature Immunology, Marson and his colleagues used CRISPR-based gene editing techniques to alter regulatory T-cells, selectively removing 40 different transcription factors.
then, the researchers focused on the 10 transcription factors that played the most important role in the initial screening and looked at thousands of genes to see which genes were turned on or off in the altered cells.
analyzed a total of 54,424 individual regulatory T-cells.
by analyzing gene groups activated or silenced by the 10 original transcription factors, the team integrated a large network of genetic procedures involved in regulating T-cell biology.
studies have shown that HIVIVEP2, a lesser transcription factor, has a strong effect on regulatory T-cell function.
follow-up study in mice, scientists found that removing the HIVIVEP2 gene reduced the ability of regulatory T cells to calm inflammation.
authors say their study demonstrates the powerful role of CRISPR gene editing and analysis of individually edited cells in the study of human biology and the genetics of human diseases.
(bioon.com) Source: Scientists map genes controlling system 'brakes' Original source: Kathrin Schumann et al, Functional CRISPR dissection of gene networks controling human regulatory T cell identity, Nature Immunology (2020). DOI: 10.1038/s41590-020-0784-4.