IBD tagged posts

Human intestinal organoids (HIOs) generated in the hydrogel matrix differentiate into mature intestinal tissue and present specialized human intestinal cell types, such as enteroendocrine cells (CHGA; red), after transplantation into an animal. Credit: Ricardo Cruz-Acuña, Georgia Tech

By combining engineered polymeric materials known as hydrogels with complex intestinal tissue known as organoids – made from human pluripotent stem cells – researchers have taken an important step toward creating a new technology for controlling the growth of these organoids and using them for treating wounds in the gut that can be caused by disorders such as inflammatory bowel disease (IBD)...

This image is a mouse intestinal organoid, or “mini-gut,” used to study epithelial cell barrier function in ongoing inflammatory bowel disease and cancer studies. Photo courtesy of Coy Allen. Credit: Virginia Tech

Could inflammatory bowel disease and colon cancer be prevented by changing the shape of a single protein? There is an intimate link between uncontrolled inflammation in the gut associated with inflammatory bowel disease and the eventual development of colon cancer. This uncontrolled inflammation is associated with changes in bacteria populations in the gut, which can invade the mucosal tissue after damage to the protective cellular barrier lining the tissue.
But Virginia Tech researchers found that modifying the shape of IRAK-M, a protein that controls inflammation, can significa...

Highlights •PKCλ/ι is required for Paneth cell differentiation •PKCλ/ι reduces EZH2 stability and promotes Atoh1 and Gfi1 expression •PKCλ/ι induces intestinal epithelial cell survival through the repression of JNK •PKCλ/ι loss enhances intestinal inflammation and cancer

A promising new target for future drugs to treat inflammatory bowel disease (IBD) has been found. The study also indicates that another protein, protein kinase C (PKC) λ/ι, may serve as a biomarker of IBD severity. “The intestine is protected by specialized cells, called Paneth cells, that secrete antimicrobial peptides,” said Jorge Moscat, Ph.D., deputy director and professor in the NCI-designated Cancer Center...

An intrinsic complement-NLRP3 axis regulates human TH1 responses. T cell receptor activation and CD46 costimulation trigger NLRP3 expression and intracellular C5a generation. Subsequent intracellular C5aR1 engagement induces ROS production (and possibly IL1B gene transcription) and NLRP3 assembly, which in turn mediates IL-1β maturation. Autocrine IL-1β promotes TH1 induction (IFN-γ production) but restricts TH1 contraction (IL-10 coexpression). C5aR2 cell surface activation by secreted C5a negatively controls these events via undefined mechanisms. Dysfunction of this system contributes to impaired TH1 responses in infection or increased TH17 responses during intestinal inflammation.

Researchers have unlocked secrets of our ancient immune system...