This week on TIBDI: Keys to Treg homeostasis are uncovered and the killing mechanism of RegIII is brought into focus.
Survival of Memory Tregs
Regulatory T cells (Treg) may be key to controlling inflammatory bowel disease (IBD). Finding the factors that drive their growth could lead to new treatments. Scientists from the University of Washington School of Medicine may now have discovered the missing clues. They found that Treg can be divided into central and memory subsets, which are located in different regions of the body and are exposed to different signals. Central memory Treg were found to express CCR7 and enter lymphoid tissues, which allowed them to thrive on IL-2. The effector memory type, on the other hand, expressed high amounts of the costimulatory molecule ICOS and survived via signals provided from dendritic cells. The balance between the two types of Treg was controlled by inflammatory signals with inflammation encouraging increased numbers of effector Treg. If one of these types of Tregs is more important for IBD, than finding ways to expand them in vivo could be a new therapy.
RegIII Kills by Pore Formation
RegIII C-type lectins are a well-known family of antimicrobial proteins that bind bacterial targets and limit their activities. Now research from the University of Texas Southwestern Medical Center shows why. Using crystal structures of RegIIIα, they show that this antimicrobial protein drills a pore into gram-positive bacteria leading to their death. Monomers of RegIIIα assemble to form a tube of approximately 100 angstroms in diameter with a pore size of 18 angstroms. Gram-negative bacteria were protected from RegIIIα pores by lipopolysaccharide. Lowered RegIII expression is associated with null NOD2 mutations, which are often found in Crohn’s disease patients.
- Mukherjee, S., Zheng, H., Derebe, M. G., Callenberg, K. M., Partch, C. L., Rollins, D., et al. (2015). Antibacterial membrane attack by a pore-forming intestinal C-type lectin, 1–16. doi:10.1038/nature12729
- Smigiel, K. S., Richards, E., Srivastava, S., Thomas, K. R., Dudda, J. C., Klonowski, K. D., & Campbell, D. J. (2013). CCR7 provides localized access to IL-2 and defines homeostatically distinct regulatory T cell subsets. The Journal of Experimental Medicine, 185(11), 6426. doi:10.4049/jimmunol.1200507