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.
- David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., et al. (2015). Diet rapidly and reproducibly alters the human gut microbiome. Nature, 505(7484), 559–563. doi:10.1038/nature12820
- Mazzini, E., Massimiliano, L., Penna, G., & Rescigno, M. (2014). Oral Tolerance Can Be Establishedvia Gap Junction Transfer of Fed Antigensfrom CX3CR1. Immunity, 1–14. doi:10.1016/j.immuni.2013.12.012
- Webster, K. E., Kim, H.-O., Kyparissoudis, K., Corpuz, T. M., Pinget, G. V., Uldrich, A. P., et al. (2014). IL-17-producing NKT cells depend exclusively on IL-7 for homeostasis and survival. Mucosal Immunology, 1–10. doi:10.1038/mi.2013.122