Sept. 7, 2017.  The study of T cells and B cells, their function, and the interaction between them that causes runaway inflammation and the progression of disease have been the subjects of numerous groundbreaking lupus investigations over the past decade.

Today, Rong Fan, PhD, from Yale University, is building on these discoveries by using his Target Identification in Lupus (TIL) grant from the Lupus Research Alliance to expand our understanding of disease progression. Drawing upon his background in biomedical engineering, Dr. Fan has developed a microchip platform to profile Follicular helper T cells (Tfh) to comprehensively analyze their function in disease pathogenesis. Dr. Fan’s hope is that his work will lead to a way of blocking these cells.

“Tfh cells may play a key role in promoting autoreactive B cell maturation in lupus,” explained Dr. Fan. “Via aberrant cytokine secretion, Tfh cells initiate B cell activation in lupus, promote tissue injury, and may serve as a perpetrator to the pathogenesis in lupus. In lay language, Tfh cells are talking to B cells and telling them what to do — we’re trying to decipher what they say.”

Dr. Fan is looking for a distinguishing feature that may serve as a biomarker to identify these potentially pathogenic cells, but the hurdle he faces is the potential polyfunctional nature of circulating Tfh cells. They can secrete an array of cytokines that can be both protective and harmful.

We hope that Dr. Fan’s pioneering work may bring clarity. The single-cell highly multiplexed cytokine-profiling microchip he developed can measure up to 42 cytokines on a single T cell. “With better diagnosis comes better outcomes,” said Dr. Fan. “The number of Tfh cells in a patient’s blood doesn’t really tell you the whole story — you need to look into their functions. That is what our technology is capable of doing.”

Clearly the Lupus Research Alliance believes in Dr. Fan’s forward-thinking approach, and he is extremely excited. “Without this support, I know I would not have been able to get my research off the ground for three years,” he shared. In fact, “funding for projects like mine is what makes innovative research possible.”

A CHAIN REACTION OF EVENTS

T cells are the immune system’s first line of defense. When they encounter bacteria, viruses, chemicals, pollen or any foreign invader, T cells release chemicals, known as cytokines, that cause B cells to multiply and release immune proteins called antibodies.

B cells are a type of white blood cell that helps the body fight infection. In lupus this process goes awry, causing the immune system to make too many antibodies. These antibodies can then attack healthy tissue.

Dr. Rong Fan is using microchip technology to uncover more about Tfh cells. His aim is to crack the lupus code.