Protein Found Vital for Controlling Inflammation in Crohn’s Disease; Possible Therapeutic Target for IBD

Protein Found Vital for Controlling Inflammation in Crohn’s Disease; Possible Therapeutic Target for IBD

Researchers have found that protein kinase C (PKC) λ/ι is an important player for maintaining intestinal epithelium balance and preventing intestinal inflammation. Patients with inflammatory bowel diseases (IBD) such as Crohn’s disease showed reduced levels of PKC λ/ι. These findings highlight a possible valid therapeutic strategy for IBD and intestinal cancer.

The study, “Control of Paneth Cell Fate, Intestinal Inflammation, and Tumorigenesis by PKCλ/ι,” was published in the journal Cell Reports.

The intestinal epithelium is composed of different types of cells, and through an orchestrated balance of interactions among these different cell types, the commensal population of microbes (called microbiota), and the immune system are key for maintaining intestinal homeostasis.

Paneth cells are a highly specialized population of intestinal epithelial cells and they are important for protecting the intestinal epithelium from intestinal pathogens, since Paneth cells store and release antimicrobial peptides. Their protective activity is also important for controlling intestinal inflammation.

In fact, alterations in Paneth cells were shown to contribute to conditions like IBDs, including Crohn’s disease and ulcerative colitis. Understating how the differentiation and function of Paneth cells is regulated is important to develop new therapies for these diseases.

A team of researchers at Sanford Burnham Prebys Medical Discovery Institute in California investigated PKC λ/ι because the function of this protein, while linked to several oncogenic and inflammatory pathways in vitro, is still largely unknown when it comes to intestinal homeostasis and pathology.

Researchers discovered that PKC λ/ι is widely expressed in the entire intestinal epithelium, and in particular in Paneth cells. They found that PKC λ/ι is required for Paneth cell differentiation and survival. Conditions where PKCλ/ι deficiency impairs Paneth cell differentiation leads to an inflammatory response. Ultimately, this is amplified by an increase in cell death in the whole intestinal epithelium, including both the small intestine and colon.

Crohn’s disease patients showed reduced PKCλ/ι levels, which correlated with impaired Paneth cell development, intestinal epithelial death, and intestinal inflammation, according to researchers.

These results show that PKCλ/ι expression is vital for controlling and inhibiting intestinal inflammation and cancer by promoting a stable number of Paneth cells.