Vagus nerve activation of the spleen shows promise to treat infections

 One of the main roles of the spleen is to help the body's immune system fight infections. The spleen does this through producing and regulating antibodies—antibody production is negatively affected in various conditions, including sepsis and autoimmune diseases such as lupus.

New research published in Science Advances by the Feinstein Institutes for Medical Research scientists shows that activation of the vagus nerve triggers the spleen, thereby regulating the production of antibodies.

This research highlights how the nervous system regulates immunity and suggests the potential for non-pharmacological vagus nerve modulation to treat a variety of diseases, such as lupus and sepsis.

This research was led by Betty Diamond, MD, director of the Institute of Molecular Medicine, in collaboration with Stavros Zanos, MD, Ph.D., associate professor in the Institute of Bioelectronic Medicine and Barbara Sherry, Ph.D., professor at the Feinstein Institutes.

They found that chronic stimulation of the vagus nerve led to a decrease in the production of specific antibodies by splenic B cells that attack and destroy foreign invaders and are able to prevent disease in the future by remembering what those substances look like. This decrease was associated with changes in the way B cells matured and survived in the body, as well as alterations in the functional organization of other immune cells.

Credit: Stavros Zanos, MD, Ph.D. and Betty Diamond, MD

Stimulating immunity through the vagus nerve

"Although we have a good understanding of the role of the vagus nerve in the regulation of the inflammatory response and the innate immune system, this study provides new insights in how the vagus nerve regulates adaptive immunity and the functions of B cells," said Dr. Diamond.

"Better understanding these mechanisms will elucidate how altered function of the vagus nerve in conditions like sepsis and autoimmune disease may impact immune function and could lead to new therapeutic approaches for these conditions."

In the study, the Feinstein Institutes' team discovered that acetylcholine released in response to vagus nerve stimulation (VNS) directly affects B cells by interacting with specific receptors on their surface, thereby altering their ability to produce signaling molecules and mature.

"Consistent stimulation of the vagus nerve in mice allows us to explore the therapeutic possibilities of bioelectronic medicine in new diseases," said Dr. Zanos. "These exciting findings warrant further investigation and eventually studies in humans to explore the extent to which vagus nerve stimulation, and other bioelectronic medicine approaches, could become treatment options for diseases involving adaptive immunity."

Research into antibodies and the vagus nerve

For more than four decades, Dr. Diamond has dedicated her career to the study of DNA-reactive B cells, autoantibodies and their origin and effect on the body. In May 2022, in recognition of her breakthrough achievements in molecular medicine and original research, The National Academy of Sciences elected Dr. Diamond as one of its newest members.

Dr. Zanos's research focus is on understanding the anatomy and physiology of the vagus nerve and the effects vagus nerve stimulation has in inflammation and cardiovascular diseases. This study builds on a 2021 paper by Dr. Zanos' group in which they described the development and characterization of the first chronic VNS implant in mice.

Dr. Zanos is leading a cross-institutional research team to develop a detailed map of the anatomy of the human vagus nerve and all its more than 100,000 fibers.

"While we understand the spleen is an essential part of the immune system, finding that stimulation of the vagus nerve affects the regulation of adaptive immunity by this critical organ is novel and important," said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes and Karches Family Distinguished Chair in Medical Research.

"The research by Drs. Diamond and Zanos highlights the need to continue producing knowledge about bioelectronic medicine's potential to treat or prevent autoimmune disease."

Chronic diseases such as arthritis, diabetes and cancer

Building on years of research in molecular disease mechanisms and the link between the nervous and immune systems, Feinstein Institutes' researchers discover neural targets that can be activated or inhibited with neuromodulation devices, like vagus nerve implants, to control the body's immune response and inflammation.

If inflammation is successfully controlled, diseases—such as arthritis, pulmonary hypertension, Crohn's disease, inflammatory bowel diseases, diabetes, cancer and autoimmune diseases—can be treated more effectively.

Beyond inflammation, using novel brain–computer interfaces, Feinstein Institutes' researchers have developed techniques to bypass injuries of the nervous system so that people living with paralysis can regain sensation and use their limbs. By producing bioelectronic medicine knowledge, disease and injury could one day be treated with our own nerves without costly and potentially harmful pharmaceuticals.

More information: Izumi Kurata-Sato et al, Vagus nerve stimulation modulates distinct acetylcholine receptors on B cells and limits the germinal center response, Science Advances (2024). DOI: 10.1126/sciadv.adn3760

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