Interleukin-37 Regulates Innate Immune Signaling in Human and Mouse Colonic Organoids
This week we profile a recent publication in Scientific Reports from
Dr. Joannie Allaire (pictured) in the laboratory of Dr. Bruce Vallance.
Can you provide a brief overview of your lab’s current research focus?
In the Vallance lab, we use patient derived-organoids (mini-guts) as pre-clinical models to understand the pathogenesis of Inflammatory Bowel Diseases as well as enteric bacterial infections. We focus on the cross-talk that occurs between the epithelial cells that line the gut and the microbes that reside nearby and how that promotes intestinal defense. As a senior postdoctoral fellow, I am establishing my own research program looking at these innate defenses in the developing intestine (in newborns and children) to find better therapies for babies suffering from intestinal inflammation.
What is the significance of the findings in this publication?
We demonstrate that IL-37, an anti-inflammatory molecule, can inhibit the inflammatory responses of human and mouse primary intestinal epithelial cells (organoids). IL-37 does this by binding to the receptor SIGIRR (expressed by epithelial cells), which leads to the inhibition of pro-inflammatory NFkB and p38 signaling. Importantly, we also demonstrate that mouse and human organoids respond differently to pro-inflammatory stimuli and their responses are also different than what was previously seen using transformed cell lines.
What are the next steps for this research?
The next step will be to examine how intestinal organoids derived from IBD patients respond to IL-37. Since we hope to be able to use IL-37 as a potential therapeutic for IBD, we need to clarify whether IL-37 can suppress inflammatory responses in cells from IBD patients. This is important since many potential therapies are tested only on cells from healthy individuals, whereas cells from IBD patients are known to show altered behavior. We are also looking at the expression of IL-37 in the intestines of children to determine if expression of IL-37 is impaired in children that develop intestinal inflammation.
This research was funded by:
CIHR, MSFHR, FRQ-S, Crohn’s and Colitis Canada.