Understanding How the Immune System Develops

The cell in the forefront is blue with lighter green protrusions on its surface. Additional T cells are visible in the background.

Scanning electron microscopy of a T cell.
Credit: Stock image

The immune system’s role is to prevent and limit infection. It carries this out through cells that have unique functions. One of these cell types is called T lymphocyte, or T cell, which helps kill infected cells and activates and recruits other immune cells. T cells mature in a small organ located right above the heart called the thymus, and the cells undergo a tightly regulated process that downregulates stem cell programming genes and upregulates T cell programming genes. These changes to the cell’s gene expression patterns are regulated by transcription factors and epigenetic factors.

In a study from the Love Lab, researchers identified an important epigenetic regulator of T cell maturation called Lsd1, which is a histone demethylase. This type of enzyme removes tags called methyl groups and thereby regulates DNA accessibility and the activity of genes. The team found that Lsd1 helps turn off stem cell programing and other gene signatures that keep T cells at an early developmental (i.e., progenitor) stage. Without Lsd1, T cell do not develop into more mature stages, and the cells acquire genetic signatures that are more commonly seen in other types of immune cells. However, the team noted that these mutated cells, which lack Lsd1, did not actually become other types of immune cells, suggesting that additional regulatory factors are needed.

Overall, the findings help establish Lsd1 as a major factor that facilitates T cell development by repressing specific genes. The authors also note that Lsd1 is often over expressed in cancer cells, and Lsd1 inhibitors are part of experimental chemotherapies. Therefore, off-target effects of these drugs ought to be examined more carefully, especially in younger patients where T cell development is ongoing.

Learn more about the Genetics and Epigenetics of Development Group: https://www.nichd.nih.gov/about/org/dir/affinity-groups/GED.

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