This week on TIBDI: A transcription factor controls Th17 plasticity and changes T cell homing, and genome wide association scans have missed the boat by not examining non-coding DNA.
T Cells, So Plastic, It’s Fantastic
T cell differentiation into subsets that have unique specializations (Th1, Th2, Th17) has been long established. What is relatively new is the idea of T cell plasticity. This is the ability of, otherwise, established T cells to change their orientation based on signals from the environment. In an attempt to learn the limits of plasticity, scientists from Albany Medical College used conditional knockouts of the transcription factor BCL11B to change the way T cells behave. They found that loss of this transcription factor caused GATA4 and IL-4 to be expressed in Th17 cells. As a result, the cells expressed gut-homing markers (α4β7) and localized to the gut lymph nodes, inducing retinoic acid production in local dendritic cells. This effect was strong enough to beneficially redirect T cells that would normally head to the central nervous system in a model of multiple sclerosis.
Non-Coding Regions and IBD
Genome wide association scans allow us to determine which genes may be mutated in patients with inflammatory bowel disease (IBD). However, these same studies didn’t just identify single nucleotide changes (otherwise known as single nucleotide polymorphisms (SNPs)) in genes alone, they also found SNPs in non-coding regions between genes. Researchers from Utrecht University asked themselves if these SNPs could be located in gene regulatory regions that were important for IBD. To answer this, they first determined active regulatory regions in IBD immune and epithelial cells, then they looked to see if SNPs were found near these regions. They found that 92 of 163 total SNPs associated with IBD were in active regulatory regions of immune and epithelial cells. This could lead to new treatments.
- Califano, D., Sweeney, K. J., Le, H., VanValkenburgh, J., Yager, E., O’Connor, W., Jr., et al. (2013). Diverting T helper cell trafficking through increased plasticity attenuates autoimmune encephalomyelitis. The Journal of clinical investigation. doi:10.1172/JCI70103DS1
- Mokry, M., Middendorp, S., Wiegerinck, C. L., Witte, M., Teunissen, H., Meddens, C. A., et al. (2013). Many Inflammatory Bowel Disease Risk Loci Include Regions that Regulate Gene Expression in Immune Cells and the Intestinal Epithelium. Gastroenterology, 1–43. doi:10.1053/j.gastro.2013.12.003