Researchers at BC Children’s Hospital and the University of British Columbia have found that special proteins called chemokines help keep our bodies’ defenses in check by preventing the immune system from mistakenly harming healthy tissue. This discovery may lead to new therapies that stop the unwanted immune attacks that cause disorders like type 1 diabetes and multiple sclerosis or lead to life-threatening organ rejection in transplant patients.
“This discovery will help us learn more about what immune pathways need to be ‘fixed’ to slow, stop or prevent the harmful immune responses that lead to autoimmune disorders,” says Dr. Megan Levings, an investigator at the Child & Family Research Institute at BC Children’s Hospital, a Professor in the University of British Columbia Department of Surgery, and lead of the study, which was published in The Journal of Clinical Investigation.
Our immune system protects against disease by destroying bacteria, viruses and other potential dangers like cancer cells. When the immune system works correctly, it attacks harmful substances while leaving healthy tissue alone. However, in autoimmune disorders, the immune system mistakenly destroys healthy parts of the body, leading to lifelong illness. In patients with organ and tissue transplants, the immune system sometimes attacks the transplanted tissue. This rejection process is difficult to treat and can be fatal.
Type 1 diabetes develops when the immune system destroys insulin-producing cells in the pancreas, making patients dependent on injections of insulin for life. The condition typically develops during childhood and affects an estimated 31,000 people in British Columbia.
Immune cells called regulatory T Cells (Tregs) usually prevent the immune attacks that cause type 1 diabetes, multiple sclerosis and other autoimmune conditions. However, scientists know relatively little about how Tregs work and why they sometimes fail to do their job.
In this study, scientists looked at samples taken from mice and found Tregs make proteins called chemokines that attract potentially harmful immune cells. Once the immune cells come into close proximity with the Tregs, the Tregs can send chemical signals that stop them from attacking healthy tissue.
Previous research has shown chemokines draw immune cells to sites of inflammation so the cells can attack pathogens and other dangerous substances. This is the first study to reveal chemokines also help prevent the immune system from harming healthy tissue.
“This is an exciting finding because it describes an unexpected way that the immune system regulates itself,” says Dr. Levings.
Scientists also compared blood samples from children with type 1 diabetes to samples from healthy children and found that Tregs in diabetic children produced fewer chemokines than Tregs from healthy children. This suggests that problems with Treg function play a role in the development of diabetes.
“This finding could help us develop new therapies that prevent or treat autoimmune disorders and tissue rejection by ensuring Tregs are making enough chemokines to work correctly,” says Dr. Levings.
This research was supported by the Canadian Institutes for Health Research and JDRF. The researchers are supported by BC Children’s Hospital Foundation, Canadian Institutes for Health Research, the Canadian Association of Gastroenterology, JDRF, and the Canadian Diabetes Association.
Patterson SJ, Pesenacker AM, Wang AY, Gillies J, Mojibian M, Morishita K, Tan R, Kieffer TJ, Verchere CB, Panagiotopoulos C, Levings MK. T regulatory cell chemokine production mediates pathogenic T cell attraction and suppression. J Clin Invest. 2016 Feb 8. pii: 83987. doi: 10.1172/JCI83987. PMID: 26854929