A protein called Zbtb46, expressed by specialized immune cells, has a major role in protecting the gastrointestinal tract from excessive inflammation, according to a study from researchers at Weill Cornell Medicine.
The finding, which appears July 13 in Nature, is a significant advance in the understanding of how the gut maintains health and regulates inflammation, which could lead to better strategies for treating diseases like inflammatory bowel disease (IBD).
“We’ve known that there are related families of immune cells in the gut that can either protect from inflammation or at other times be major drivers of inflammation,” said senior author Dr. Gregory Sonnenberg, associate professor of microbiology and immunology in medicine in the Division of Gastroenterology & Hepatology, and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. “This new finding helps us understand how these cells are regulated to optimally promote intestinal health and prevent inflammation.”
IBD, which includes Crohn’s disease and ulcerative colitis, affects several million people in the United States. These chronic inflammatory disorders target the gut, can be seriously debilitating, and treatments may not work well for some patients—mainly because scientists don’t have a complete picture of what is driving these diseases and how the sophisticated immune cell networks in the gut support tissue health.
Dr. Sonnenberg’s laboratory has been advancing the science of gut immunity with studies of recently identified immune cells called ILC3s. These “innate lymphoid cells” are related to T cells and B cells, and clearly have important roles in protecting the gut and other organs from excess inflammation. However, in the context of IBD or colorectal cancer they become altered. In general, scientists have wanted to know more about how these cells work.
Drs. Gregory Sonnenberg and Wenqing Zhou. Provided by Sonnenberg lab
To this end, Dr. Sonnenberg and his team, including first author Dr. Wenqing Zhou, a postdoctoral researcher in the Sonnenberg Laboratory, set out to make a detailed catalog of ILC3s and other related immune cells residing in the large intestine of mice, using relatively new single-cell sequencing techniques.
A surprise finding was that a subset of ILC3s express Zbtb46, an anti-inflammatory protein that prior studies had suggested is produced only in dendritic cells, a very different type of immune cell. The researchers showed in experiments with mice that ILC3s expressing Zbtb46 have a strong ability to restrain inflammation following gut infection. When they blocked Zbtb46 expression in ILC3s, gut infection led to signs of severe inflammation, including a rise in the numbers of other gut immune cells promoting inflammation. To read further, please click here.