STAT5 and BATF Promote Chromatin Accessibility in Helper T Cells

The human immune system is made up of a complex set of biological processes and mechanisms that help our bodies fight against pathogens. When a foreign stimulus enters our body and slips past our innate immune cells, the immune system sends lymphocytes as a more advanced approach to attack.

There are 2 types of lymphocytes: B cells and T cells -- both of which mark the pathogen and create a tailored response to destroy it. B cells achieve this by producing antibodies specific to the pathogen to neutralize the threat, whereas cytotoxic T cells produce powerful enzymes that induce cell death.

Perhaps the most important part of the lymphocyte response belongs to the helper T cell (Th). Th cells help activate B cells and T cells by creating small proteins called cytokines, providing a blueprint for the lymphocytes to follow.

In order for Th cells to be effective in the immune response, they must be differentiated. Th cell differentiation is a lineage-based process that can be reversed and will vary depending on the immune response needed. It begins when cytokine signals and transcription factors open up the chromatin, allowing a group of transcription proteins called STAT to dictate which type of helper T cell it becomes.

In a study out of Indiana University, a team of researchers examined Th9 cells—a particular subset of Th cells constant in the immune response of humans and mice. These cells demonstrate antitumor activity, and help promote immunity to certain parasites and allergies.

The team led by Drs. Yongyao Fu and Mark Kaplan wanted to determine the factors that allow Th9 cells to produce a cytokine called interleukin-9 (IL-9), which aids cell proliferation and prevents apoptosis. Specifically, they focused on transcription factors STAT5 and BATF, and how they affect chromatin accessibility and gene expression, with hopes of finding potential therapies for IL-9-dependent immune response.

The researchers performed a ChIP-seq on Th9 cells and identified BATF as a required factor in cell development and IL-9 production, but they discovered that BATF could only access the IL9 gene in a euchromatin state.

To determine the role STAT5 plays in accessibility of the IL9 gene, the researchers isolated Th9 cells from human peripheral blood mononuclear cells. In total, they collected between 0.4 million and 1 million Th9 cells. They added a STAT5 inhibitor on day 1 and monitored the cells for 5 days. On day 5, the team used the EpiQuik Chromatin Accessibility Kit to determine the chromatin state.