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.
- Fuss, I. J., Joshi, B., Yang, Z., Degheidy, H., Fichtner-Feigl, S., de Souza, H., et al. (2014). IL-13R 2-bearing, type II NKT cells reactive to sulfatide self-antigen populate the mucosa of ulcerative colitis. Gut. doi:10.1136/gutjnl-2013-305671
- Xiao, B., Laroui, H., Viennois, E., Ayyadurai, S., Charania, M. A., Zhang, Y., et al. (2014). Nanoparticles with Surface Antibody Against CD98 and Carrying CD98 Small Interfering RNA Reduce Colitis in Mice. Gastroenterology, 1–66. doi:10.1053/j.gastro.2014.01.056