by Leigh MacMillan
Interleukin-33 (IL-33) drives inflammatory responses in allergic and nonallergic disease. Epithelial cells in the lungs, gastrointestinal tract and elsewhere release IL-33, which activates the ST2 receptor on immune cell targets.
In addition to the ST2-binding domain, IL-33 contains a nuclear chromatin-binding domain, suggesting that it may act inside cells that produce it. However, a cell-intrinsic role for IL-33 has not been established.
Matthew Stier, MD, PhD, Stokes Peebles, MD, and colleagues have now identified IL-33 expression, but not ST2 receptor expression, in developing B cells in the bone marrow (mature B cells produce antibodies). They demonstrated that IL-33 deficiency resulted in increased numbers of developing B cells.
The researchers detected IL-33 during early B cell development in humans and found reduced IL-33 expression in B cell chronic lymphocytic leukemia samples compared to healthy controls.
The findings reported in the Sept. 15 Journal of Immunology establish a cell-intrinsic role for IL-33 in early B cell development that is independent of the ST2 receptor.
This research was supported by grants from the National Institutes of Health (AI145265, AI124456, AI111820, AI145397, AI095227, AI114262, CA226432, DK084246, GM007347, RR029557, TR000445) and the U.S. Department of Veterans Affairs.