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Dr. Sonnenberg and Colleagues Discover Unique Subset of ILC3s and a Connection to Inflammation

Dr. Gregory Sonnenberg

Dr. Gregory Sonnenberg and colleagues have published a paper in Nature that has uncovered a subset of ILC3s called inflammatory ILC3s.

It is known that ILC3s, a set of immune cells (group 3 innate lymphoid cells), help the immune system to tolerate beneficial microbes and suppress inflammation in the intestines and other organs in the body. In their pivotal paper published in Nature on December 1, 2021, Dr. Sonnenberg and colleagues uncovered (in a mouse model) a subset of ILC3s cells (inflammatory ILC3s) that have the opposite effect in multiple sclerosis (MS) and other brain disorders. This research suggests that countering the activity of these newly discovered cells, which circulate in the bloodstream and can infiltrate the brain, could lead to a therapeutic approach for such conditions. MS alone affects more than two million people worldwide.

In addition to discovering the subset of inflammatory ILC3s in the central nervous system of mice, the researchers also found that inflammatory ILC3s spurred another group of immune cells, called T cells, to attack myelinated nerve fibers and leading to MS-like symptoms. The team also found similar inflammatory ILC3s 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,” explains senior author Dr. Sonnenberg, Associate Professor of Microbiology and Immunology in Medicine, Division of Gastroenterology and Hepatology, WDOM, and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

Other key findings from the study included that the removal of ILC3s from the mouse model essentially blocked the cells’ ability to activate myelin-attacking T cells, and that ILC3s residing in other tissues in the body can be programmed, in effect, to counter the activity of brain-infiltrating T cells, thus preventing the MS-like condition disease in mice.

This study was carried out by The Sonnenberg Laboratory at Weill Cornell Medicine and in collaboration with Dr. Ari Waisman, Director, Institute for Molecular Medicine, University Medical Center of Johannes Gutenberg University Mainz.

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