Tag Archives: NKT cells

Ulcerative Colitis’ NKT Cells and Nanoparticle siRNA

Nanoparticles may be a new way to transport active molecules to specific cells in IBD patients.
This week on TIBDI: Interleukin-13-producing NKT cells may be behind ulcerative colitis, and nanoparticle transport of CD98 small interfering RNAs may offer new treatment options for IBD.

An NKT Cell Antigen for Ulcerative Colitis

Ulcerative colitis (UC) is well known for its association with Th2 responses. More recently, it was found that IL-13-producing, Type II NKT cells accumulate in a rodent model of UC. Furthermore, these studies showed that IL-13 is cytotoxic for the epithelial cells and increases the killing activities of NKT cells. Dr. Ivan J Fuss of the National Institutes of Health continued this work in human UC patients. He found that the NKT cells accumulate in the lamina propria and when exposed to the self-antigen lyso-sulfate begin to secrete large amounts of IL-13 and upregulate IL-13Rα2 (IL-13 receptor). The authors speculate that these cells could be the main drivers of UC inflammation and that a key pathologic event in UC may be the abnormal expression of lyso-sulfate by gut epithelial cells in response to signals from microbiota.

Nanoparticles for the Treatment of IBD

Small interfering RNAs (siRNAs) offer the possibility of treating IBD by silencing disease-related genes. However, carriers are needed to bring these molecules to the cytoplasm of the correct cells. Dr. Bo Xiao of Georgia State University found success delivering CD98 siRNA to CD98+ gut cells by using orally administered nanoparticles coated with a targeting antibody and polyethylene glycol, which allows the particles to enter the mucus layer and reach the immune cells below. CD98 is part of the amino acid transporter LAT1, which amplifies integrin signaling and supports immune cell activation. The research team was able to successfully use their system to reduce the symptoms of two colitis models.


Diet in IBD and Gut Antigen Collection Explained

High Fat Foods - NCI Visuals Online
An animal-based, high fat diet can lead to microbiota changes that may increase IBD development.
This week on TIBDI: Macrophages and dendritic cells work together to collect antigens in the gut, diet could influence inflammatory bowel disease development, and interleukin-7 maintains natural killer T cells.

Capturing Antigen Takes Two in the Gut

Oral tolerance, immune tolerance against ingested antigens, may influence the chronic nature of inflammatory bowel disease (IBD). Finding out how antigen is picked up in the gut and presented to T cells to initiate regulatory mechanisms could lead to new therapies. Now Elisa Mazzini of the European Institute of Oncology in Italy has found that in the small intestine antigen uptake leading to oral tolerance requires teamwork between macrophages and dendritic cells. Macrophages expressing the chemokine receptor CX3CR1 were exceptional in collecting soluble antigens by sticking dendrites between epithelial cells towards the lumen. They then transferred their antigen loads to neighboring dendritic cells expressing CD103, which have the abilities to initiate oral tolerance. Dr. Mazzini found that the transfer required the expression of the gap junction protein connexin 43, which allowed appeared to allow the transfer of entire peptide-MHC complexes.

Diet in IBD

The populations of microorganisms in the human gut are known to change during IBD. However, it’s unknown if there are specific changes that could initiate IBD development. A study by Dr. Lawrence A. David from Harvard University shows how easily the intestinal microbiota is changed by diet. Volunteers on an animal-based diet had significant changes in their populations as soon as one day after the diet reached the gut. Moreover the gene expression and activity of the intestinal residents were also altered. Those with an animal-based diet had increases in Bilophila species, which is associated with the development of intestinal inflammation in mice. The authors suggest that animal-based diets could contribute to the development of IBD.

IL-7 and NKT Cell Survival

Interleukin (IL)-7 is a cytokine that helps the long-term survival of Th17 cells and innate lymphoid cells that express the transcription factor RORγt. It is suspected to be important for maintaining populations of T cells that induce and propagate IBD. Dr. Kylie Webster from the Garvan Institute in Australia has now increased IL-7’s circle of influence. She found that IL-7 also maintains natural killer T (NKT) cells that produce IL-17. IL-7, using the PI3K/AKT/mTOR pathway. IL-7 caused the NKT cells to proliferate in vivo. Because more IL-7 is produced in response to bacterial triggers. Dr. Webster speculated that NKT cells may use IL-7 to quickly respond to bacterial pathogens.