This week on TIBDI: Soluble CD83 may be a useful anti-inflammatory factor, bacterial proteomics reveals new Crohn’s disease biomarkers, and GATA3 is an important transcription factor for group 3 innate lymphoid cells.
Soluble CD83, the Anti-Inflammatory Molecule
In order to control signals of membrane-bound receptors, the body often employs soluble versions that act as ligand sponges, preventing signaling on the stationary, active molecule. This is also the case with the pro-inflammatory, co-stimulatory molecule CD83, which is expressed on activated dendritic cells as well as activated T and B cells. The researcher Jenny Eckhardt, located at the University Hospital Erlangen in Erlangen, Germany, realized that this process might be involved in controlling intestinal inflammation and sought more answers with her team. They found that administration of soluble CD83 prevented colitis in a mouse model of inflammatory bowel disease. This was associated with improvements in many inflammatory mediators. They also determined that the positive effects of soluble CD83 were induced by indoleamine 2,3-dioxygenase, which is known to have immunosuppressive properties.
Metaproteomics for Crohn’s Disease Monitoring
Catherine Juste of the French National Institute for Agricultural Research (INRA) has zeroed in on new molecular parameters for Crohn’s disease (CD), which may impact future diagnosis, monitoring and treatment. While many have focused on categorizing the intestinal microbiota signatures of CD patients, her team went one step further and looked at the microbial protein signature. They found that many proteins from Bacteroides species were over represented. Many of the over-expressed proteins were for the invasion and breaching of the mucosa. This unique method of looking at bacterial proteins could lead to new targets to help treat CD.
GATA3’s New Identity
GATA3 is a transcription factor most well known for its role in inducing T cell differentiation towards Th2. However, Nicolas Serafini of the Pasteur Institute and French Institute of Health and Medical Research (INSERM) has now found that GATA3 has many more uses including the induction of group 3 innate lymphoid cells (ILC3). ILC3 are essential for generating a wave of epithelial cell-activating IL-22 after intestinal bacteria infection. ILC3 are also characterized by the expression of the Th17-associated transcription factor RORγt. GATA3 was necessary for these cells during development, and their loss led to a reduced resistance against an intestinal bacterial pathogen.
- Eckhardt, J., Kreiser, S., bbeler, M. D. O., Nicolette, C., DeBenedette, M. A., Tcherepanova, I. Y., et al. (2014). Soluble CD83 ameliorates experimental colitis in mice, 1–13. doi:10.1038/mi.2013.119
- Juste, C., Kreil, D. P., Beauvallet, C., Guillot, A., Vaca, S., Carapito, C., et al. (2014). Bacterial protein signals are associated with Crohn’s disease. Gut. doi:10.1136/gutjnl-2012-303786
- Serafini, N., Klein Wolterink, R. G. J., Satoh-Takayama, N., Xu, W., Vosshenrich, C. A. J., Hendriks, R. W., & Di Santo, J. P. (2014). Gata3 drives development of RORγt+ group 3 innate lymphoid cells. The Journal of Experimental Medicine. doi:10.1084/jem.20131038