CRISPR Study Maps Networks That Help Differentiate Regulatory T Cells

Researchers have mapped out the networks of genes that help differentiate regulatory T cells from other T cells. The collaborative team—from Gladstone Institutes, UC San Francisco and the Technical University of Munich—published their results in Nature Immunology. 

"Piecing together the genetic networks that control the biology of regulatory T cells is a first step toward finding drug targets that change the function of these cells to treat cancer and autoimmune diseases," says Alex Marson, senior author of the study.

In the new study, scientists used CRISPR-based gene-editing technology to alter regulatory T cells, selectively removing any of 40 different transcription factors. The 40 transcription factors were chosen because previously published data had already hinted that they might perform specific functions in the regulatory cells compared to other T cells. The researchers then focused on the 10 transcription factors that had the strongest effect in this initial screen, and looked across tens of thousands of genes to see which ones were turned on or off in the altered cells. In total, they performed this analysis on 54,424 individual regulatory T cells.

By analyzing the subsets of genes activated or silenced by these transcription factors, the team put together vast networks of genetic programs involved in the biology of regulatory T cells. Among the most surprising results, the study revealed that the transcription factor HIVEP2 has a strong effect on regulatory T cell function. In follow-up studies in mice, the scientists found that removing the HIVEP2 gene reduced the ability of the regulatory T cells to reduce inflammation.

"Now, we can theoretically take any specialized cell from the body and start removing individual genes and study the consequences on the cells in much finer detail than ever before," says Marson. "This really opens up human cells removed from the body as a tractable experimental system."