Understanding the role of GARP in immune tolerance
Results from a recent study looking at the role of the protein GARP in immune tolerance was published in JCI Insight earlier this month. Lead author Caroline Wallace, Ph.D. describes in this Hollings Cancer Center (HCC) Lab Chat series how this study helps set the stage to better understand the immune system and how the findings may apply to diseases such as cancer and autoimmunity.
What was unique about the study and what did you find?
B cells regulate many biological functions, including helping fight infections, while maintaining tolerance to food and self-tissues. We looked at the role of GARP in B cells as the functions of this protein had not been previously studied in this immune population. We discovered that when B cells properly express GARP, normal B cell function is maintained. Without GARP, we found that spontaneous autoimmune disease occurred.
Why is this important?
One of the most exciting findings from the study was the importance of GARP in B cells found in the gut compared to other parts of the body. Without GARP, the number of B cells expanded, producing more antibodies, which led to a loss of tolerance. For example, most of us don’t have reactions to what we eat because of multiple biological regulatory functions that are in place. We found that GARP is an additional regulatory protein that B cells use to protect the body against abnormal cell activity.
What’s next for this research?
The discovery that GARP regulates B cell tolerance can also be applied to other diseases, such as cancer. We need to better understand the role of B cells in GARP in the tumor microenvironment. In cancer, you need the immune system to fight the disease. If there is too much immune suppression, which GARP likely affects, that changes the body’s ability to fight the cancer.
Want to know more?
Wallace is a recent Ph.D. graduate in the laboratory of Zihai Li, M.D., Ph.D., a cancer immunologist at HCC at the Medical University of South Carolina (MUSC). Li serves as chair of MUSC’s Department of Microbiology and Immunology and is co-leader of the Cancer Immunology Research Program at HCC, South Carolina’s only National Cancer Institute-designated Cancer Center. The Li laboratory studies the mechanisms that regulate both the adaptive and innate immune systems and how they function in cancer and autoimmune disease.