New Way to Reprogram Lymph Node Function to Fight Multiple Sclerosis

    Researchers from the University of Maryland, Fischell Department of Bioengineering (BIOE) and the University of Maryland, School of Medicine report a new technique for turning off the harmful immune attack that occurs during autoimmune diseases such as multiple sclerosis (MS), while keeping healthy functions of the immune system intact.

    “Our lab is combining immunology and nanotechnology to reprogram how the immune system responds to self-cells in the brain that are mistakenly attacked during MS,” said Christopher Jewell, Ph.D., BIOE assistant professor, and corresponding author on the new report. “The finding, conducted in cells and preclinical animal models of MS, could lead to new approaches for reversing paralysis in MS, or better therapies for other autoimmune diseases.”

    The group’s study (“Reprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen Specific”) was published in Cell Reports. According to a collaborator, Jonathan Bromberg, M.D., Ph.D., from the University of Maryland, School of Medicine, “The studies show it is possible to treat and cure inflammatory disease with a single dose of therapeutics loaded in biodegradable polymers targeted directly to lymph nodes–the tissues that coordinate immune function in the body.”

    In MS, the immune system incorrectly recognizes myelin, which insulates and protects nerves fibers in the brain. Immune cells enter the brain and attack, leading to slow loss of motor function and other complications. Current therapies for MS work by decreasing the activity of the immune system; but they do so in a broadly suppressive way that often leaves patients vulnerable to infection. There are also no cures for MS, type 1 diabetes, and other autoimmune diseases.

    “The goal of our work—and that of others in the field—is to expand cells that are both myelin-specific and regulatory in nature,” said Lisa Tostanoski, first author on the paper. “The hope is that these cells can directly suppress inflammation without targeting healthy immune function.”

    Dr. Jewell’s team is working to reprogram the function of lymph nodes: Instead of generating inflammatory cells that attack myelin, the lymph nodes are “instructed” to promote regulatory immune cells that control the attack against myelin. To carry out the reprogramming, degradable polymer particles that incorporate regulatory signals are delivered to lymph nodes using a unique intra–lymph node injection technique. Once in the lymph nodes, these particles slowly release immune signals to promote regulatory immune cells that mature and migrate to the central nervous system to suppress the attack against myelin.

    Test their strategy, the team is using two rodent models of MS. The results are promising thus far, demonstrating that a single particle treatment can permanently reverse paralysis. Importantly, these effects were found to be myelin specific and correlated with local changes in the function and types of cells in lymph nodes and the central nervous system.

    “Moving forward, our team is working to show the therapeutic effects result from repair and remyelination in the brain,” said Dr. Jewell. “That represents a goal that is a critical criterion to improve on human MS therapies.”