With ‘innovator award,’ Iwasaki will explore possible cause of lupus
Yale immunologist Akiko Iwasaki has received a grant from the Lupus Research Alliance (LRA) that will allow her to investigate the possible cause of lupus, a chronic, complex autoimmune disease that affects millions of people worldwide.
The LRA’s 2023 Dr. William E. Paul Distinguished Innovator Award (DIA) provides up to $1 million over four years for projects that explore “bold, paradigm-shifting ideas that could lead to groundbreaking discoveries in lupus research.”
Iwasaki is the Sterling Professor of Immunobiology and professor of dermatology and of molecular, cellular, and developmental biology at Yale School of Medicine, professor of epidemiology (microbial diseases) at Yale School of Public Health, and an investigator at the Howard Hughes Medical Institute.
The award will enable Iwasaki and her team to study whether the immune system’s reaction to viruses can trigger lupus.
“Lupus is an autoimmune disease, which means that our immune system attacks our own cells by mistake,” she said. “Exactly what is being targeted by the immune system still remains a mystery. We hypothesize that immune reaction to viruses that live inside of our cells may be the culprit. We are developing the right tools to be able to probe this link, thanks to the support of LRA.”
For the project, Iwasaki will aim to uncover how ancient viral remnants in our DNA, called endogenous retroviruses (ERVs), trigger autoimmune responses in systemic lupus erythematosus (SLE). ERVs, which resemble historical records of past viral infections, make up approximately 8% of the human genome, a genetic legacy from viruses that infected human ancestors millions of years ago.
Molecules that cause inflammation called type I interferons are normally produced in response to viral infection but are increased in many people with SLE. What causes this increase, however, is not well understood. Recent findings from Iwasaki’s lab suggest that these ERVs become active and drive an increase in type I interferons. In this study, she will evaluate the immune response to increased ERV levels as a trigger of autoimmunity in SLE.
In lupus, T cells, the “guards” of the immune system, can become autoreactive, mistakenly identifying the body’s own cells as foreign. These autoreactive T cells can also activate B cells to produce autoantibodies that recognize the body’s own organs and tissues rather than harmful invaders like viruses and bacteria.
Iwasaki will measure ERV levels and identify and characterize autoreactive T cells targeting ERVs in samples from individuals with cutaneous lupus, which affects the skin. To better understand the immune system’s response to ERV activation, she will use a mouse model to determine how increased ERV activation in the skin drives inflammation and autoimmunity. By establishing a connection between endogenous retroviruses, inflammation, and autoreactive T cells in lupus, this research has the potential to lead the way to new, targeted therapies for this complex condition.
