T helper 17 Cell Induction in the Human Gut
It’s easy to forget with the all the mouse immunology research that many things about gut Th17 cells haven’t been described with human cells. Now we are one step further. The journal Gastroenterology has an article in press that describes the induction of Th17 cells from human-derived, lamina propria cells. Using cells isolated from Crohn’s disease patient and control intestinal samples, Japanese scientists found an antigen-presenting cell population with a monocyte/macrophage lineage that was extremely good at inducing Th17 cells from naïve T cells. While both patient and control cells both could induce Th17, Crohn’s disease patient cells were the most effective. Th17 cells are suggested to play a role in Crohn’s disease, and this result supports this idea even more.
Bacteria and Nociceptors, Talking Together
Most of us have heard the term, “the second brain,” when people are referring to the neural networks within the intestinal system. Sensory neurons called nociceptors are responsible for the pain sensation. During intestinal Staphylococcus aureus infection, pain is induced, and, for a long time, it was assumed to be caused inflammatory mediators interacting with the pain neurons. Chiu et al, in the most recent issue of Nature, have now shown that, in actuality, it’s the bacteria that are directly activating the nociceptors. Furthermore, in neuron ablation experiments, they discovered that the nociceptors could influence inflammation. Interestingly, the communication wasn’t via pattern recognition receptors. Instead, the communication mediators were formylated peptides and α-haemolysis, a pore-forming toxin, produced by S. aureus. In the future, it will be interesting to find out how friendly commensals interact with nociceptors. They could form a novel way of modulating the immune response during intestinal inflammation.
Choosy Pre-Dendritic Cells Choose Retinoic Acid
Retinoic acid has a variety of effects within the gut-associated immune system, and it is known to influence the generation of different kinds of dendritic cells (DCs). However, it wasn’t known precisely when retinoic acid was having an effect on DC generation from pre-DCs or how it was affecting systemic DC populations. Scientists from the National Institute of Health now know the answer to both questions. They found that a retinoic acid deficiency caused a reduction in pre-DC-derived conventional DCs in both the spleen (CD11b+CD8α-Esamhigh DCs) and the gut (CD11b+CD103+ DCs), while populations of several other DC types were not affected. By transferring pre-DCs to different hosts with different retinoic acid levels, the scientists determined that ambient retinoic acid levels controls the fate of pre-DC. As conventional DCs are necessary for sufficient protective immune responses, this highlights the importance of vitamin A (precursor of retinoic acid) supplementation during mucosal stress.
- Chiu, I. M., Heesters, B. A., Ghasemlou, N., Hehn, Von, C. A., Zhao, F., Tran, J., et al. (2014). Bacteria activate sensory neurons that modulate pain and inflammation. Nature, 501(7465), 52–57. doi:10.1038/nature12479
- Klebanoff, C. A., Spencer, S. P., Torabi-Parizi, P., Grainger, J. R., Roychoudhuri, R., Ji, Y., et al. (2013). Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells. The Journal of experimental medicine, 43(2), 1608. doi:10.1172/JCI200214989
- Ogino, T., Nishimura, J., Barman, S., Kayama, H., Uematsu, S., Okuzaki, D., et al. (2013). Increased Th17-Inducing Activity of CD14+CD163low Myeloid Cells in Intestinal Lamina Propria of Patients with Crohn’s Disease. Gastroenterology, 1–47. doi:10.1053/j.gastro.2013.08.049