August 5, 2021

Researchers at St. Jude Children’s Research Hospital identified the series of molecules that guide a sub-set of immune cells, which may be key for future vaccine improvements and autoimmune therapies. These findings, published online July 7, 2021 in Nature, were funded in part by the Lupus Research Alliance (LRA).

The immune system uses T cells to kill pathogens – bacteria or viruses – on or inside cells, and B cells to produce antibodies to destroy pathogens circulating in the blood. T follicular helper (T_FH) cells are a specialized subset of T cells that help B cells produce antibodies. CXCR5, a protein on the surface of T cells, is necessary for these T_FH cells to work properly. Prior to this research, it was unknown which molecules control CXCR5 protein levels specifically in T_FH cells.

Using highly powerful genetic screening techniques, Hongbo Chi, PhD, and colleagues aimed to find a pathway – the series of molecules that work together in sequence to guide cell development and functions – that shapes maturation and roles of T_FH cells. They found that the CDP-ethanolamine pathway was the key pathway controlling T_FH cell development and function, including how T_FH cells trigger antibodies. This pathway generates a molecule called phosphatidylethanolamine, which impacts the stability and function of the CXCR5 protein.

This intricate discovery has broad significance for therapies that modulate – either strengthen or suppress – the immune system. The CDP-ethanolamine pathway may be targeted for therapies to fine-tune T_FH cell responses. A well-functioning immune system is carefully calibrated to attack pathogens while ignoring the body’s own healthy cells. For example, strengthening the CDP-ethanolamine pathway in T_FH cells has the potential to boost a person’s immune response to a vaccine, making the vaccine more effective. In autoimmune patients, where antibodies attack a person’s own cells, reducing the activity of the CDP-ethanolamine pathway may decrease harmful antibody production. Further studies are being conducted to explore these possible approaches to new treatments.

“Understanding how T_FH cells are regulated at the molecular level opens up doors for new therapies for autoimmune diseases like lupus. When we understand the molecular pathways, we can find precise molecules to target to amplify or suppress the immune system. We thank the Lupus Research Alliance for the research funding support,” said Dr. Chi, Robert G. Webster Endowed Chair in Immunology at St. Jude Children’s Research Hospital.