Inhibiting the activity of group 3 innate lymphoid cells could serve as a new therapeutic approach for neurologic conditions.
Certain group 3 innate lymphoid cells (ILC3s)—immune cells that typically protect against gastrointestinal inflammation—may have the opposite effect in multiple sclerosis (MS) and other brain inflammation-related conditions, according to a study published in Nature. The investigators said these results suggest that inhibiting the activity of these cells could serve as a new therapeutic approach for neurologic conditions.
While studying ILC3s in a mouse model of MS, the investigators discovered a unique subset of ILC3s that circulate in the bloodstream and can enter the brain. These ILC3s—named inflammatory ILC3s—caused T cells to attack myelinated nerve fibers, leading to MS-like disease symptoms. Similar inflammatory ILC3s were found in the peripheral blood and cerebrospinal fluid of MS patients.
“This work has the potential to inform our understanding of, and potential treatments for, a broad variety of conditions involving T-cell infiltration of the brain,” said Gregory Sonnenberg, PhD, associate professor of microbiology and immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, in a press release.
According to the investigators, inflammatory ILC3s present bits of myelin protein—the primary component of the insulating layer around nerve fibers—to T cells. This prompts the T cells to attack myelin and cause the nerve damage that gives rise to disease signs. By removing MHCII from the inflammatory ILC3s, a key component normally used in the antigen-presenting process, the investigators were able to block the cells’ ability to activate myelin-attacking T cells.
“Despite our very best disease-modifying therapies for MS, patients continue to progress, and since disease onset is early in life, they face the prospect of permanent physical and cognitive disability,” said Tim Vartanian, MD, PhD, professor of neuroscience in the Feil Family Brain and Mind Institute at Weill Cornell Medicine, chief of the division of multiple sclerosis and neuro-immunology and a professor of neurology in the Department of Neurology at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, in the release. “Identification of inflammatory ILC3s with antigen presentation capabilities in the central nervous system of people with MS offers a new strategic target to prevent nervous system injury.”
The investigators also found that they were able to effectively program ILC3s in other tissues to counter the activity of brain-infiltrating T cells, which prevented the MS-like condition in mice. They said that this study points to the possibility that MS and potentially many other inflammatory conditions could be treated by directly inhibiting the activity of inflammatory ILC3s that infiltrate the brain or by targeting self-antigens to the intestinal ILC3s that promote tolerance in other tissues.
Novel immune cell population may trigger inflammation in multiple sclerosis and other brain disorders [news release]. EurekAlert; December 1, 2021. Accessed December 3, 2021. https://www.eurekalert.org/news-releases/936550